Title of Invention

COMPOUNDS FOR DECREASING ACTIVITY OF HORMONE-SENSITIVE LIPASE

Abstract The present invention relates to a compound of the general formula II wherein R<sup>1</sup> is C<sub>1</sub>-<sub>6</sub>-alkyl optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R<sup>2</sup> is phenyl optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C<sub>1</sub>-<sub>6</sub>-alkyl, C<sub>2</sub>-<sub>6</sub>-alkenyl, aryl, heteroaryl, C<sub>3</sub>-<sub>5</sub>-heterocyclyl and C<sub>3</sub>-<sub>10</sub>-cycloalkyl; R<sup>3</sup> is hydroxyl substituted with pyridyl wherein said pyridyl is substituted with piperidyl wherein said piperidyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C<sub>1</sub>-<sub>6</sub>-alkyl, C<sub>3</sub>-<sub>6</sub>-alkenyl, aryl, heteroaryl, C<sub>3</sub>-<sub>5</sub>-heterocyclyl and C<sub>3</sub>-<sub>10</sub>-cycloalkyl; and X is 0; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable thereof, and a process for preparing the same. The present invention also relates to a composition comprising the compound of general formula II.
Full Text COMPOUNDS AND USES THEREOF FOR DECREASING ACTIVITY OF HORMONE-SENSITIVE LIPASE.
FIELD OF THE INVENTION
The present invention relates to compounds, compositions containing them, and their use for treating medical disorders where it is desirable to modulate the activity of hormone-sensitive lipase.
BACKGROUND OF THE INVENTION
The overall energy homeostasis of a mammalian system requires a high degree of regulation to ensure the availability of the appropriate substrate at the appropriate time. Plasma glucose levels rise during the post-prandial state, to return to pre-prandial levels within 2-3 hours. During these 2-3 hours, insulin promotes glucose uptake by skeletal muscle and adipose tissue and decreases the release of free fatty acids (FFA) from adipocytes, to ensure that the two substrates do not compete with each other. When plasma glucose levels fall, an elevation in plasma FFA is necessary to switch from glucose to fat utilization by the various tissues.
In individuals with insulin resistance, FFA levels do not fall in response to insulin, as they do in normal individuals, preventing the normal utilization of glucose by skeletal muscle, adipose and liver. Furthermore, there is a negative correlation between insulin sensitivity and plasma FFA levels.
Hormone-sensitive lipase (HSL) is an enzyme, expressed primarily in adipocytes, that catalyses the conversion of triglycerides to glycerol and fatty acids. It is through the regulation of this enzyme that the levels of circulating FFA are modulated. Insulin leads to the inactiva-tion of HSL with a subsequent fall in plasma FFA levels during the post-prandial state, followed by the activation of the enzyme when the insulin concentration falls and catecholamines rise during the post-absorptive period. The activation of HSL leads to an increase in plasma FFA, as they become the main source of energy during fasting.

The activation inactivation of HSL is primarily mediated through the cAMP-protein kinase A and AMP-dependent kinase pathways. There are compounds like nicotinic acid and its derivatives, that decrease the activation of HSL via these pathways and cause a decrease in lipolysis that leads to a reduction in the FFA levels. These drugs have a beneficial effect in the utilization of glucose and in the normalization of the excess triglyceride synthesis seen in patients with elevated FFA. However, since these pathways are used by other processes in the body, these drugs have severe side effects.
We have found compounds that specifically inhibit the lipolytic activity of HSL and lead to a decrease in plasma FFA levels. These compounds can be used to treat disorders where a decreased level of plasma FFA is desired, such as insulin resistance, syndrome X, dyslipi-demia, abnormalities of lipoprotein metabolism.
One object of the present invention is to provide compounds and pharmaceutical compositions that inhibit the lipolytic activity of HSL. A further object is to provide compounds which have good pharmaceutical properties such as solubility, bioavailability etc.
DEFINITIONS
The following is a detailed definition of the terms used to describe the compounds of the invention.
"Halogen" designates an atom selected from the group consisting of F, CI, Br and I.
The term "C1-6-ralkyl" in the present context designates a saturated, branched or straight hydrocarbon group having from 1 to 6 carbon atoms. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, tert-pentyl, n-hexyl, isohexyl and the like.
The term "C1-6-alkyl" in the present context designates a saturated, branched or straight hydrocarbon group having from 2 to 6 carbon atoms. Representative examples include, but are not limited to, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, n-hexyl, isohexyl and the like.

The term "C1-6-alkoxy"in the present context designates a group -O-C1-6-alkyl wherein C1-6alkyl is as defined above. Representative examples include, but are not limited to, methoxy, eth-oxy, n-propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy,tert-butoxy, n-pentoxy, isopen-toxy, neopentoxy, terf-pentoxy, n-hexoxy, isohexoxy and the like.
The term "C3-C6alkoxy" in the present context designates a group -O-C1-6-alkyl wherein C3-8-alkyl is a saturated, branched or straight hydrocarbon group having from 3-6 carbon atoms. Representative examples of C1-6-alkoxy include, but are not limited to, n-propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, tert-pentoxy, n-hexoxy, isohexoxy and the like.
The term "C2-6-alkenyl" as used herein, represent an olefinically unsaturated branched or straight hydrocarbon group having from 2 to 6 carbon atoms and at least one double bond. Examples of such groups include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, allyl, iso-propenyl, 1,3-butadienyl, 1-butenyl, hexenyl, pentenyl and the like.
The term "C1-6o-cycloalkyl" as used herein represents a saturated mono-, bi-, tri- or spirocar-bocyclic group having from 3 to 10 carbon atoms. Representative examples are cyclopropyl, cyclobutyl, cyclopentyl, cydohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, bicy-do[3.2.1]octyl, spiro[4.5]decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like.
The term "C1-6-heterocydyr as used herein represents a saturated 3 to 8 membered ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Representative examples are pyrrolidyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, aziridinyl, tetrahydrofuranyl and the like.
The term "aryl" as used herein represents a carbocyclic aromatic ring system being either monocydic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenan-threnyl, fluorenyl, indenyl, pentaienyl, azulenyl, biphenylenyl and the like. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-iimiting examples of such partially hydrogenated derivatives are 1,2,3,4-tetrahydronaphthyl, 1,4-dihydronaphthyl and the like.
The term "aryioxy" as used herein represents an aryl which is linked via an oxygen atom, e.g. phenoxy, 1-naphthyloxy, 2-naphthyloxy and the like.

The term "heteroaryl" as used herein represents a heterocyclic aromatic ring system containing one or more heteroatoms selected from nitrogen, oxygen and sulfur such as furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyI, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyI, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyi, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyI, tetrazolyl, thiadiazinyl, indolyl, isoindolyl, benzofuranyi, benzothiophenyl (thianaphthenyl), indazolyl, benzimidazolyl, benzthiazolyl, ben-zisothiazolyl, benzoxazolyl, benzisaxazolyl, purinyl, quinazolinyl, quinolizinyl, quinolinyl, iso-quinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, azepinyl, diazepinyl, acridinyl and the like. Heteroaryl is also intended to include the partially hydrogenated derivatives of the heterocyclic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 2,3-dihydrobenzofuranyl, 3,4-dihydroisoquinolinyl, pyrrolinyl, pyra-zolinyl, indolinyl, oxazolidinyl, oxazolinyl, oxazepinyl and the like.
The term "perhalomethyl" as used herein designates a methyl moiety substituted with three halogen atoms. Non-limiting examples of perhalomethyl are CF3, CCI3,and CF2CI.
The term "perhalomethoxy" as used herein designates a perhalomethyl linked via an oxygen atom, e.g. -0-CF3, -O-CCI3, and -0-CF2CI
The term "ring system" as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and they encompass moieties with zero, one or more hetereatoms selected from nitrogen, oxygen and sulphur. Non-limiting examples of such ring systems are aryl, C3-6-heterocyclyl and heteroaryl.
The term "heterocyclic system" as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and containing in their ring structure one or more heteroatoms selected from nitrogen, oxygen and sulfur. Non-limiting examples of such heterocyclic systems are C3-6-heterocyclyl and heteroaryl.
Certain of the above defined terms may occur more than once in the structural formulae, and upon such occurrence each term shall be defined independently of the other.

The term "optionally substituted" as used herein means that the groups in question are either unsubstituted or substituted with one or more of the substituents specified. When the groups in question are substituted with more than one substituentthe substituents may be the same or different.
The term "optionally covalently bound" as used herein means that the substituents in question are either not covalently bound to each other or the substituents are directly connected to each other by a covalent bond. A non-limiting example of such optionally covalently bound substituents is -NR1R2 wherein R1 is ethyl and R2 is propyl which provided that the substituents, ethyl and propyl, are optionally covalently bound may be ethyl-propyl-amino, 1-piperidyl, 3-methyM-pyrrolidyI or2,3-dimethyI-1-azetidyl.
The term "hydrolysable group" as used herein means a group which can be hydrolysed at certain chemical conditions, i.e. an internal covalent bond in the group can be cleaved to give two compounds. A hydrolysable group does not have to be hydrolysed during carrying out the present invention. For instance, the hydrolysable group -C(=X)-L. can be hydrolysed to give the products -C(=X)OH and HL, which means that the covalent bond between -C(X) and L is cleaved. Examples of hydrolysable groups are carbamates, esters and amides.
The terms "disease", "condition" and "disorder" as used herein are used interchangeably to specifiy a state of a patient which is not the normal physiological state of man.
The term "treatment" as used herein means the management and care of a patient having developed a disease, condition or disorder, as well as the management and care of an individual at risk of developing the disease, condition or disorder prior to the clinical onset of said disease, condition or disorder. The purpose of treatment is to combat the disease, condition or disorder, as well as to to combat the development of the disease, condition or disorder. Treatment includes the administration of the active compounds to prevent or delay the onset of the symptoms or complications and to eliminate or control the disease, condition or disorder as well as to alleviate the symptoms or complications associated with the disease, condition or disorder.
The term "effective amount" as used herein means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment.

The term "modulate" as used herein means to influence, i.e. to modulate a parameter means to influence that parameter in a desired way. Examples are to modulate insulin secretion from beta cells and to modulate the plasma level of free fatty acids.
The term "medicament" as used herein means a pharmaceutical composition suitable for administration of the pharmaceutically active compound to a patient.
The term " pharmaceutically acceptable" as used herein means suited for normal pharmaceutical applications, i.e. giving rise to no adverse events in patients etc.
DESCRIPTION OF THE INVENTION
The present invention relates to compounds of the general formula II

wherein R1 is selected from Chalkyl, C2-C6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and
R2 is selected from C2-C6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C2-C6-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C2-C6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C2-C6-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C2-C6-alkyl, C2-5-alkenyl, aryl, heteroaryl, C3-6-heterocyclyl and C2-C6-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C2-C6-alkyl, C26-alkenyl, aryl, heteroaryl, C3-10heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C2-C6-alkyl, C2-C6alkenyl, aryl, heteroaryl, C2-C6-heterocydyl and C3-10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C2-C6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C2-C6-heterocyclyl and C2-C6o-cycioalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C2-C6-alkyl, C2-6-alkenyI, aryl, heteroaryl, C2-C6-heterocyclyl and C3-10-cycloalkyl is optionally substituted

with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyciyl and C3. 10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C1-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
R3 is selected from hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-aIkenyI, aryl, heteroaryl, C3. 8-heterocyclyl and C1-6o-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3_1D-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryi, heteroaryl, C1-6-heterocyclyl and C1-6o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-8-h6terocyclyl and C3_1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-6-heterocyclyI and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C1-6o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C1-6o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
X is O or S; or
a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs.

In an aspect of the invention, compounds are of the general formula III

wherein R1a and R28 are independently selected from C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C1-1o-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyt, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C2-8-alkenyl, aryl, heteroaryl, C3-8 heterocyclyl and C1-6o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano and nitro, C1-6 alkyl, C2_6-alkenyI, aryl, heteroaryl, C1-6-heterocyclyl and C1-6o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2-C6-aIkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perha-lomethoxy; and
wherein R1a is optionally covalently bound to R2a by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1a and R23 are bound; and
R4*, R53, R53 and R7a are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-aIkenyI, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted by one or more substituents selected from hydroxy, sulfanyl, sulfo, oxo, amino, cyano, nitro, C1_6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C1-6o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C1-6o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perhalomethoxy; and

A1a is N or C-R8a; A23 is N or C-R9a; A3a is N or C-R10a; A48 is N or C-R11a; and A5a is N or O R12a; and
wherein R8a, R9a, R10a, R11a and R12a are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, Cu-alkenyl, aryl, heteroaryl, C3-8-heterocyctyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and C3-10-cycloaIkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8alkyl, C2-C8-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10rcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8cpcycloatkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perha-lomethyl and perhalomethoxy.
In one embodiment, the invention is concerned with compounds of formula (III), wherein R2a is phenyl, optionally substituted by halogen or methyl.
In! another embodiment, the invention in concerned with compounds of formula (III), wherein R1a is selected from methyl and ethyl, optionally substituted by one or more halogen.
In another embodiment, the invention in concerned with compounds of formula (III), wherein
R1a and R23 are covalently bound so as to form a ring system with the N-atom to which they
are bound, wherein said ring system is a piperidine, piperazine, morpholine, or thiomor-
pholine.
In another embodiment, the invention in concerned with compounds of formula (III), wherein
R4a, R53, R6a and R7a are independently selected from hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy,
-C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perha-
lomethyl.
In another embodiment, the invention in concerned with compounds of formula (III), wherein
A1a, A23, A3a, A43 and A53 are independently selected from N, CH, CF, C-Cl and C-CF3.
In an aspect of the invention, compounds are of the general formula IV


wherein R1b and R25 are independently selected from C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaikyl, each of which may optionally be substituted with one or more substituents selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyi, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, Cn-e-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-aikyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy;
wherein R1b is optionally covalently bound to R2" by an ether, thioether, C-C or ON bond, to form a ring system with the N-atom to which R1b and R2b are bound;
R4t and R6b are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, suifo, C1-6-alkyl, C2-C6-alkenylI aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyis optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, perhalomethyl and perhalomethoxy;

R4b and R7b are independently selected from hydrogen, hydroxy, suifanyl, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, amino, sulfo, C1-6-alkyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, suifanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, C1-6-alkyI, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyI, perhalomethyl and perhalomethoxy; and

wherein R8b, R9*, R10b, R11b and R12b are selected from hydrogen, hydroxy, suifanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, amino, sulfo, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, amino, sulfo, C1-6-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, perhalomethyl and perhalomethoxy;
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4b, R5b, R6b, R7b, R8b, R9b, R10b, R11b and R12b.
In one embodiment, the invention is concerned with compounds of formula IV, wherein Ra is phenyl, optionally substituted by halogen.
In another embodiment, the invention is concerned with compounds of the general formula IV, wherein Rlb is selected from methyl and ethyl, optionally substituted by one or more halogen.
In another embodiment, the invention is concerned with compounds of the general formula IV, wherein R1b and R2b are covalently bound so as to form a ring system with the N-atorn to

which they are bound, wherein the ring system is a piperidine, piperazine, morpholine, or
thiomorpholine.
In another embodiment, the invention is concerned with compounds of the general formula
IV, wherein R4b, R56, R6b and R7* are independently selected from hydrogen, F, CI, C3-8-alkyl,
C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)-rOH, hydroxy, amino and
perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
IV, wherein A1b, Aa, A3", A46 and A5b are independently selected from N, CH and CF.
In an aspect of the invention, compounds are of the general formula V

wherein R40, R5c, R60, R7c and Rte are independently selected from hydrogen, hydroxy, sul-fanyl, amino, halogen, cyano, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl. C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyi, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8rheterocyclyi and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy,

C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha-lomethoxy; and
R9c, R10c, R11ct R12c and R13c are independently selected from hydrogen, sulfanyl, amino, halogen, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaikyl, wherein each of sulfanyl, amino, sulfo, C3-8-alkyl,, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky), C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl. C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl- C1-6alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3_10-cycloalkyl, perhalomethyl and perha-lomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R40, R5c, R6c, R7c and R30; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9c, R10c, R11c, R12c and R13c; and
at least one of R40, R5c, R60, R7c, R8cf R9c, R10c, R11c, R12c and R13c are different from hydrogen.
In one embodiment, the invention is concerned with compounds of formula V, wherein R90,
R10c, R11c, R12c and R13c are selected from H and F.
In another embodiment, the invention is concerned with compounds of the general formula V,
wherein R40, R5c, R6c, R7c and R4tc are independently selected from hydrogen, F, CI, C1-6-alkyl,
C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0);rNH2, -NH-S(=0)2-OH, hydroxy, amino and
perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula V,

where there are no covalent bonds between any of the substituents R9c, R10c, R11c, R12c and
R13c.
In another embodiment, the invention is concerned with compounds of the general formula V,
where there are no covalent bonds between any of the substituents R40, R5c, R6c, R7c and R8c.
In an aspect of the invention, compounds are of the general formula VI

wherein R4* and R5d are independently selected from hydrogen, hydroxy, suifanyl, amino, C2. 8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, amino, C2-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8crcycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkylf C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycIoalkyl, perhalomethyl and perhalomethoxy: and
R6d, R7d, R4t1, R9*, R10d, R11d, R12d, R13d and R14d are independently selected from hydrogen, hydroxy, suifanyl, halogen, amino, cyano, nitro, sulfo, C2-C8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, suifanyl, amino, suifo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-

cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-aIkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-8i0-cycloalky( may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycfyl and C3-10-cycioalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C1-6-alkoxy, C2-C8-aIkenyl, aryl, heteroaryl, C3-8-heterocycIyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy:
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4*, R5*, R4t. R7d, Red and R9d; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10d, Rl1d, R12d, R13d and R14d.
In one embodiment, the invention is concerned with compounds of the general formula VI, wherein R4t6 and R5d are H.
In another embodiment, the invention is concerned with compounds of the general formula VI, wherein R6d, R7d, Rad and R9are selected from the group consisting of hydrogen, F, CI, Chalkyl, d-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2s -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula VI, wherein R10d, R11d, R12d, R13d and R14d are selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula VI, wherein there are no covalent bonds between any of the substituents R4δH R5d, Red, R7d, RM and R9d.
In another embodiment, the invention is concerned with compounds of the general formula VI, wherein there are no covalent bonds between any of the substituents R10d, R11d, R12df R13d and R14d.


wherein R46 is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, Chalky), C1-6-alkoxy, C2-C8-alkeny!, aryl, heteroaryl, C3-10rheterocyclyl and C3-10-cycloalkyl, wherein each of C2-C8-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-10-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo,C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha-lomethyl and perhalomethoxy: and
R5e is selected from hydrogen, F, cyano, C3-8-alkyl, C3-8-alkoxy, C2-C6-aikenyi, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and Cs-to-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, and C3-8urcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op-

tionally be substituted with one or more substituents independently selected from hydroxy, suffanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl, C3-8a-cycloalkyl, perhalomethyl and perhalomethoxy;
wherein R46 and R56 may be covalently bound to each other by a C-0 bond.
In one embodiment, the invention is concerned with compounds of the general formula VII, wherein R46 or R56 is selected from the group consisting of

wherein R66, R7e, R88, R9e and R10e are independently selected from hydrogen, hydroxy, sul-fanyi, sulfo, halogen, amino, cyano, nitro, C3-8alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, .. aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-C6-aikenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8alkenyl.
In another embodiment, the invention is concerned with compounds of the general formula VII, wherein R46 or R5e is selected from the group consisting of


wherein R66, R7e, R88, R98 and R108 are independently selected from hydrogen, hydroxy, suifanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8 alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, Chalkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C1-6-alkoxy and C2-C8-aIkenyl.
In another embodiment the invention is concerned with compounds of the general formula VII, wherein at least one of the substituents R6e, R7e, R8e, R9e and R10e are selected from the group consisting of F and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula VII, wherein R48 and R5e are connected by a C-0 bond to form the compound

. wherein R11e is selected from hydrogen, hydroxy, suifanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, amino, sulfo, C1-6-alkylt C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and dMo-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8j-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-

alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaikyl, perhalomethyl and perhalomethoxy; and
R12e is selected from hydrogen, F, CI, C1-6-alkyl, C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2rOH, hydroxy, amino and perhalomethyl.

wherein R4f, Rm, R6*, R7f, Rw and R10f are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, d-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6 alkyl, Ci.6-alkoxy, C2„6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, Cn-e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that R4f and R5f are not both methoxy, and

Rw is selected from hydrogen, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8 heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C3-8alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-iQ-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkylf C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, Cwrheterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and Ca.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1_6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycioalkyl, perhalomethyl and perhalomethoxy;
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4tf R5*, R6f, R7f and Rw; and
wherein there may optionally be a covalent bond between R9* and R10f.
In one embodiment, the invention is concerned with compounds of the general formula VIII,
wherein R9f and R10f are covalently bound so as to form a ring system with the C-atom to
which they are bound.
In another embodiment, the invention is concerned with compounds of the general formula
VIII, wherein said ring system is a cycloalkyl, phenyl, heteroaryl, piperidine, piperazine, mor-
pholine, orthiomorpholine.
In another embodiment, the invention is concerned with compounds of the general formula
VIM, wherein R4f and Rw are connected by a C-O bond to form the compound

wherein R11f is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyI, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, het-

eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8alkoxy, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
R17f is selected from hydrogen, F, CI, C3-8-alkyl, 1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl; and
wherein there may optionally be a covalent bond between R9f and R10f. In an aspect of the Invention, compounds are of the general formula IX

wherein R49, R59, R69, R79, Rag, R", R109 and R11g are independently selected from hydrogen, hydroxy, sulfanyi, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independent/y selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1D-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl. heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and

R129 is selected from the group consisting of-C(=0=, -C(=0)NH-, -CHr, -CH2CH2-, -CHR15fl-, -CH2CHR159-, -CHR159-CH2-, -NH-, -NR159-, -NHC(O)-, -NR159-C(=0)-, -0-, -S-, -S(=OK -S(=0)r;
wherein R159 is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, ni-tro, C1-6-alkyl, C3-8-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl. wherein each of hydroxy, suffanyf, suffo, amino, C1-6-alkyl, C1-6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and Cs.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, CWalkyl, C3-8-alkoxy, C2-C6-alkenyl, perhalomethyl and perhalomethoxy, and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R49, R5g, R60, R79 and R15g; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R8g, R", R109f R11fl and R15g; and
R13fl is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C3-8-alkyl, Ci_ 6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8Krcycloalkyl, wherein each of C3-8-alkyl, C2-8aJkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyi, aryl, heteroaryl, C3-8-heterocyclylr and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1. 6-aIkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8afkyl, C1-6-alkoxy, C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-10-heterocydyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and

R14fl is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C2-6-alkyl, d-s-alkoxy, C3-8alkenyl, aryl, heteroaryl, heterocyclyl and C3-10-cycloalkyl, wherein each of C2-C8-alkyl. C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2_8-alkenyl, aryl, heteroaryl, C3-8heterocyciyi, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, d-6-alkoxy, C1-6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, d-r-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, perhalomethyl and perha-lomethoxy: and
wherein R13g and R14g may optionally be covalently bound to each other.
in one embodiment, the invention is concerned with compounds of the general formula IX,
wherein R139 and R149 are covalently bound so as to form a ring system with the N-atom to
which they are bound.
In another embodiment, the invention is concerned with compounds of the general formula
IX, wherein said ring system is a piperidine, piperazine, morpholine, orthiomorpholine.
In another embodiment, the invention is concerned with compounds of the general formula
IX, wherein there are no covalent bonds between any of the substituents R4°, R5g, R6g, R?B
and R15g.
In another embodiment, the invention is concerned with compounds of the general formula
IX, wherein there are no covalent bonds between any of the substituents R89, R99, R109, R11g
and R159.
In another embodiment, the invention is concerned with compounds of the general formula
IX, wherein R49, R59, R6g, R7g, R8g, R", R109, R11g are selected from the group consisting of
hydrogen, F, CI, C1-6-alkyl, C1-6-alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-
OH, hydroxy, amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula X


wherein R4h and R5th are independently selected from cyano, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C2-C6-aikenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and 03.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6~alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R6h, R7h, Rah, R9*, R10h, R12h, R14h and R15h are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and (Vio-cycloalkyl. wherein each of C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo,.halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkylf C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo,

halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R11h and R13h are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, perhalomethyl, perhalomethoxy, C3-8-alkyl, methoxy, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyl, amino, C2-C6-alkyl, C1-6-alkoxy, C3-8e-alkenyl, aryl, heteroaryl, Cwheterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10-cycloalkyl- wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4h, R4t. R6h, R™ R8h, R9h; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10h, R11h, R12h, R13h, R14h and R15h.
In.one embodiment, the invention is concerned with compounds of the general formula X, wherein R6h, R7*, R8h, R9h, R10h, R12h and R14h are selected from the group consisting of hydrogen, F, CI, C1-6-alkyl, C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula X, wherein there are no covalent bonds between R4h, R5h, R6h, R7*1, R8h and R9h. In another embodiment, the invention is concerned with compounds of the general formula X, wherein there are no covalent bonds between R10h, R11h, R12h, R13h, R14h and R15h. In another embodiment, the invention is concerned with compounds of the general formula X, wherein R15h is hydrogen. In another embodiment, the invention is concerned with compounds of the general formula X,

wherein R11h and R13h are selected from the group consisting of hydrogen, F, CI, C2-C6-aIkyl, methoxy, C3-8-alkoxy, -NHC(=0-OHI -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula XI

Rs is selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C3-8-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R51, R71, R4t, R9i, R10i, R14i and R15 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyli C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op-

tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocycfyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3_10-cycloalky[, perhalomethyl and pertia-lomethoxy: and
R111 and R13i are independently selected from hydrogen, hydroxy, sulfanyi, sulfo, halogen, amino, cyano, nitro, C3-8-allcyl, methoxy, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyi, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-ic-cycloalkyI, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-rheterocydyI, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, . heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R12 is selected from hydrogen, hydroxy, sulfanyi, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyi, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, F, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy.
In one embodiment, the invention is concerned with compounds of the general formula XI, wherein R61, Rr', R81 and R9i are selected from the group consisting of hydrogen, F, CI,C1-6-

alkyl,. C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydraxy, amino and perhalomethyi.
In another embodiment, tine invention is concerned with compounds of the general formula XI, wherein R10i, R11i, R12, R13i and R14i are selected from the group consisting of hydrogen, F, CI, C1-6-alkyl, C3-8-alkoxy, -C(=0)NH2- -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0);rOH, hydroxy, amino and perhalomethyi.
In another embodiment, the invention is concerned with compounds of the general formula XI, wherein R1S is hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula XI, wherein R10i, R11i, R12i( R1*, R141 and R15i are selected from the group consisting of H, F and methyl.

wherein R4*, Rg, R6j, R7*, R8j, R4t1 and R10j are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, het-eroaryl, C3-8-heterocyclyl and C3-10ncycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C3-8-aikenyl, aryl, heteroaryl, C-3-8a-rheterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenylf aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl. C1-6-alkoxy, C3-8alkenyi, aryl, heteroaryl, C3-8-heterocyclyl and C3-10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8-alkoxy, C3-8-alkeny!, aryl, heteroaryl, C3-8-heterocyciyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-

tro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be a covalent bond between the substituents R6J and R71; and
wherein there may optionally be a covalent bond between R5 and R8i; and
R11iand R12J are independently selected from cyano, C3-8-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-B-alkenyl, aryl, heteroaryl, pδH-heterocyclyl, and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C3-8alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
with the proviso that R9j and R10i are both hydrogen, there may optionally be a covalent bond connecting R11jand R12i.
In one embodiment, the invention is concerned with compounds of the general formula XII, wherein Ffi, Rg, R6j and R71 are selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the genera! formula XII, wherein at least one of the substituents R4i, R5j, R6j and R71 are different from hydrogen. In another embodiment the invention is concerned with compounds of the general formula XII, wherein R8i is covalently bound to R5.
In an aspect of the invention, compounds are of the general formula XIII


wherein R4k is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C1-6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-to-cycloalkyl, perhaiomethyl and perhalomethoxy: and
R5kis selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocycly! andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-10-

heterocydyl and CsMo-cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that when R4* is hydrogen, then R5kis not C(=0)N(Me)2; and
R4t R7", R8q, R9kf R10k, R11k, R13k and R14k are independently selected from hydrogen, hydroxy, suifanyl, sulfo, halogen, amino, cyano, nitre, C3-8alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryi, C3-8rheterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryi, C1-6-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl, and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R12k is selected from hydrogen, hydroxy, suifanyl, sulfo, halogen, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryi, C1-6-heterocyclyl and d-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sutfo, C3-8-alkyl, C1-6-alkoxy, C2-C6*alkenyl, aryl, heteroaryi, C3-s-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci.6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryi, C1-6-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be a covalent bond between any of the substituents selected from the group consisting of R4k, R5k, R7" and R8k; and
wherein there may optionally be a covalent bond between R5kand any one of the substituents R7* and R8k; and

wherein there may optionally be one or more covalent bonds between R10\ R11k, R12k, R13k and R14k.
In one embodiment, the invention is concerned with compounds of the general formula XIII,
wherein the substituents R4** and R5k are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XIII, wherein the substituents R5kand R8k are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XIII, wherein the substituents R10k and R11k are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XIII, wherein the substituents R12k and R13k are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XIII, wherein R6k, R™, R8k and R5kkare selected from the group consisting of hydrogen, F, CI,
hydroxy, amino, methyl, methoxy, ethoxy and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XIII, wherein R10k, R11\ R12k, R13k and R14k are selected from the group consisting of hydro-
gen, F, CI, C3-8-alkyl,, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH,
hydroxy, amino and perhalomethyl.

wherein R1 is Ci.e-alkylF C2-C6-alkenyl or C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and
R2 is C1-6-alkyl, C3-8-alkenyl, arylf heteroaryl, C3-8-heterocyclyl, or C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3. 10-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, C1-6-alkyl, C2-C6-

alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6alkyl, C3-8alkenyl, aryl, heteroaryl, C3-s-heterocyclyi and C3-10-cycloalkyi, wherein each of hydroxy, sulfanyl, amino, Chalkyl, C2-C6-alkenyl, aryi, heteroaryl, C3-8-heterocyclyl and C3-810-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, perha-lomethyl and perhaiomethoxy; with the proviso that when R1 and R2 are identical they are not methyl or benzyl; and
R2 is optionally covalently bound to R1 by an ether, thioether or C-C bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
R9, RQ!, R8!, R9(, R10' and R11] are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-6-aIkeny!, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, Cve-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-10-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cswrheterocyclyi, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo,C1. 8-aikyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhaiomethoxy: and
R41 and R71 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, methoxy, C3-6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyl, sulfo, amino, C3-8-alkyl, C3-alkoxy, C2-C6-aikenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkoxy, C2-ralkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, perhalomethyl and perhaiomethoxy: and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R41, Ra, R61, R71, Rai, R91, R101 and R111.
In one embodiment, the invention is concerned with compounds of the general formula XIV,
wherein R1 and R2 are covalently bound so as to form a ring system with the N-atom to which
they are bound.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein said ring system is a piperidine, piperazine, morpholine, or thiomorpholine.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein there are no covalent bonds between R1 and R2.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein there are no covalent bonds between R8' and any of the substituents selected
from the group consisting of R9i, R101, R111.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein there are no covalent bonds between R81 and any of the substituents selected
from the group consisting of R4!, R51, R61 and R71.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein there are no covalent bonds between any of the substituents R41, R51, R61, R71,
R81, R91, R101 and R111.
In another embodiment, the invention is concerned with compounds of the general formula
XIV, wherein R4', R51, R61 and R7i are selected from the group consisting of hydrogen, F, CI,
C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2f -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy,
amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula XV


wherein R4"1 is selected from hydrogen, sulfo, C3-8-alkyl, C2-C6-alkenyII aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-afkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from 'hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cs-a-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyir aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha-lomethoxy: and
R5m, R6m, R7m, R8m, R9"1, R10m, R11m, R12m, R13m, R14m, R15mand R16m are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl,, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo,C1-6-alkyl,C1-6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of RAm, R5™, R6m, R7m and R8m; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9"1, R10m, R11m, R12m, R13m, R14m, R15mand R16m.
In one embodiment, the invention is concerned with compounds of the general formula XV,
wherein there are no covalent bonds between any of the substituents selected from the
group consisting of R5*, R6ro, R7m and R8m.
In another embodiment the invention is concerned with compounds of the general formula
XV, wherein there are no covalent bonds between any of the substituents R9m, R10m, R11m,
R12m and R13m.
In another embodiment, the invention is concerned with compounds of the general formula
XV, wherein there are no covalent bonds between any of the substituents R14m, R15mand
R16m.
In another embodiment, the invention is concerned with compounds of the general formula
XV, wherein R4m is covalently bound to R6m.
In another embodiment, the invention is concerned with compounds of the general formula
XV, wherein R5m, RBm, R7m, R8m, R9"1, R10m, R11m, R12m, R13m and R14mare selected from the
group consisting of hydrogen, F, CI, C3-8-alkyl, C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -
S(=0);rNH2l -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XV, wherein R14m, R15m and R16m are selected from the group consisting of hydrogen, F, CI,
C3-8-alkyt, C1-6-alkoxy, -C(=0)NH2, -NHC(=OK-H, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy,
amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula XVI


wherein R4" is selected from hydrogen, sulfo, C2-C8-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C2-C6-alkyIt C3-8alkenyl, aryl, heteroaryl, Csn-heterocyclyl and C3.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C-14-alkyl, C3-8-alkoxy, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-crcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-hetero-cyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10"cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
Z is selected from S, S(=0) and S(=0)2; and
R5n, R6", R7n, R8n, R9n, R10n, R11n, R12n, R13n and R14n are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocydyl and

C3-icrcycloa!kyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfa, Ct_6-alkyl, C1-6 alkoxy, C2-C6-alkenylr aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perha-lomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4", R5n, R6n, R7n and R8nf; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10n, R11n, R12n and R14n; and
at least one of the substituents R5n, R6n, R7n, R8n, R9n, R10n, R11n, R12n, R13n and RUn are different from hydrogen.
In one embodiment, the invention is concerned with compounds of the general formula XVI, wherein there are no covalent bonds between any of the substituents R5n, R6n, R7n and R8n. In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein there are no covalent bonds between any of the substituents R10n, R11n, R12n. In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R14nis not covalently bound to any other substituent selected from the group consisting of R4n, R5n, R6n,. R7n, R8n, R10n, R11n, R12n.
In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R4n is covalently bound to R6n.
In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R5n, RBn, R7n and R8" are independently selected from the group consisting of hydrogen, F, CI, C3-8alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R14nis selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, d-c-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.


wherein R20 is selected from sutfo, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyt and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substitu-ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3.io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclylf and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1_6-alkyl, C1-6«alkoxy, C2-C8-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3. icrcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2_6-aikenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, G2δHalkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhaiomethoxy; with the proviso that R20 is not methyl; and
R40, R5D, R60 and R70 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8r heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl,

C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3 8-alkyl, C3-8alkoxy, C2-C6alkenylt,aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
A10 is N or C-R60; A20 is N or OR90; A30 is N or C-R100; A40 is N or C-R110; and A50 is N or C-R12°; and
wherein R8°, R90, R100, R110 and R120 are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8r heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, G2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3_B-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, perhalomethyl and perhalomethoxy; with the proviso that
when A10, A20, A3°, A40 and A50 are all CH, and R40, R50, R60 and R7D are all hydrogen, then R20 is not phenyl; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R40, R5°, R60, R70, R80, R90, R10D, R110 and R120
In one embodiment, the invention is concerned with compounds of the general formula XVII, wherein there are no covalent bonds between any of the substituents R40, R50, R60 and R7°. In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein there are no covalent bonds between any of the substituents A10, A20, A30, A40 and A50.

In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein R5kis selected from the group consisting of cycloalkyl, phenyl, piperidine, piperazine, morpholine, thiomorpholine and heteroaryl.
In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein R40, R50, R8° and R70 are independently selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-afkoxy, -C(=0)NH2) -NIHC(=0)-OH, -S(=0}2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula XVIII
(XVII I)
wherein R4p is selected from hydrogen, sulfo, C2-C8-alkyl, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C2-C6-alkyl, C2-C6a!kenyl, aryl, heteroaryl, C3-8heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyI, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl,wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyf, aryl, heteroaryl, C3-8-heterocyclyl, C3. lo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-8crcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl,

oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8alkoxy, C2-C6-alkenylI aryl, heteroaryl, C3-8-heterocyclyl, C3-10rcycloaIkyl, perhalomethyl and perhalomethoxy: and
R5p, R6p, R7p and R8p are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, C3-8-alkyl, C1-6-aIkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloaIkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-aIkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl,C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
R9p, R10p, R11p, R12p, R13p, R14p, R15pand R1Bp are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6alkenyi, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5p, R6p and R7p; and
wherein there may optionally be a covalent bond between R4p and R5p so as to form a chromen ring system; and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9p, R10p, R11p, R12p, R13p, R14p, R15pand R16p; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)r, -NR17p- and -CR17pR18p-;and
wherein R17p and R18p are independently selected from hydrogen, hydroxy, sulfanyi, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyi, sulfo, amino, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, and C3-8icrcycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1. 6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaikyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and p3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl, C3-10-cycloaIkyl, perhalomethyl and perhalomethoxy.
In one embodiment, the invention is concerned with compounds of the general formula XVIII,
wherein E is selected from the group consisting of-O and -CR17pR18p-.
In another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein R4p and R5p are connected by a covalent bond so as to form said chromen
ring system.
In another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein R4p and R59 are connected by a covalent bond so as to form the chromen ring
system


wherein R19p is selected from the group consisting of hydrogen, hydroxy, sulfanyl, sulfa, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, suffo, amino, Chalkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfa, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, perhalomethyl and perhalomethoxy.
In another embodiment, the invention is concerned with compounds of the general formula XVlll, wherein R4p is selected from the group consisting of

wherein R20p, R21p, R229, R23* and R24p are independently selected from hydrogen, hydroxy, sulfanyl, sulfa, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3_10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfa, amino, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfa, oxo, halogen, amino, cyano, nitro, sulfa, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, perhalomethyl and perhalomethoxy.
In another embodiment, the invention is concerned with compounds of the general formula XVlll, wherein there are no covalent bonds between any of the substituents R4p, R5p, R6p, R7p and R8p.

In another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein there are no covalent bonds between any of the substituents R9p, R10p, R11p,
R12p( R13p, R14p, R15pandR16p.
in another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein R10p and R11p are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein R9p, R10p/R11p, R12p, R13p, R14p, R15pand R16p are independently selected from
hydrogen, F, CI, C3-8alkyl, C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0);rNH2, -NH-S(=0)r
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XVIII, wherein R5**, R6p, R7p and R8p are independently selected from hydrogen, F, CI, C1-6-
alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino
and perhalomethyl.

wherein R4*, RBq, R7q, R5kR10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q,and R18q are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi and C3-8icrcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8r

heterocyctyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, rheterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-aikyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R5kand R5kkare independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, Br, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and d-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, d-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4", R5q, R6q, R7q and RBq; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9q, R10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q and R1Bq.
In one embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4q and R6q are connected by a covalent bond.

in another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4k is selected from the group consisting of substituted heteroaryl and substituted C3-8-heterocyclyl.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R5k is selected from the group consisting of

wherein R19q, R20q, R21q, R22* and R23q are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkylf wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C1_6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3. 10-cycloalkyl, perhalomethyl and perhalomethoxy.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein there are no covalent bonds between any of the substituents R4q, R5q, R6q, R7q and R8q.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein there are no covalent bonds between any of the substituents R9q, R10q, R11q, R12q, R13q, R14q, R15q' R16q, R17q and R18q.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R10p and R11p are connected by a cbvalent bond.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R11p and R13p are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4t R10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q and R18q are independently selected from hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2| -NHC(=0)-OH, -S(=0)2-NH2, -NH«S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4t. R10q, R11q, R12q, R14q, R15q, R16q, R17q and R1Bq are all hydrogen or F. In another embodiment the invention is concerned with compounds of the general formula XIX, wherein R59, R6q, R7q and R8q are independently selected from hydrogen, F, CI, C3-8-alkyl, C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.

wherein R4t is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C3-8-alkoxy, C3-8-alkenyl, aryl, het-eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-aIkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-

10-cycloalkyl, perhaiomethyl and perhalomethoxy: provided that R4ris not methyl or phenyl; and
R4t R6r, R7r( R4t. R4tf R10r, R11rf R12r, R13r, R14r, R15r, R18r, R17r and R18r are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci-ralkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, Cwrheterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ct-6-alkyI, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhaiomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5r, R6r, R7r and R8r; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9r, R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17r and R1Br.
In one embodiment, the invention is concerned with compounds of the general formula XX, wherein R4t and R51" are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R4r is selected from the group consisting of substituted heteroaryl and substituted C3-8-heterocyclyl.


wherein R19r, R2r, R21r, R2b and R2b are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3.B~heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyI, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, C3-10-cycloalkyl, perha-lomethyl and perhalomethoxy.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein there are no covalent bonds between any of the substituents R5r, R61", R7r and
R8r.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein there are no covalent bonds between any of the substituents R4t. R?0r, R11r, R12r,
R13rf R14r, R15rand R16r.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein R10r and R11r are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein R11r and R13r are connected by a covalent bond.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein R9r, R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17r and R1Br are independently selected
from hydrogen, F, CI, C1-6alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-
S(=0)?-OH, hydroxy, amino and perhaiomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein R9r, R10r, R11r, R12r, R14r, R15r, R16r, R17r and R18r are all hydrogen or F.
In another embodiment, the invention is concerned with compounds of the general formula
XX, wherein R5r, R8r, R7r and R4t are independently selected from hydrogen, F, CI, C3-8-alkyl,

C3-8-alkoxy, -C(=0)NHa, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
In an aspect of the invention, compounds are of the general formula XXI

wherein A1s is N or C-R17s; A25 is N or C-R18s; A35 is N or C-R19s; A4s is N or C-R205; and A56 is N or C-R21s; and
wherein R17!\ R1Bs, R19s, R205 and R21s are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-8K,-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyI, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C3-8alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and

R5s, R6s, R7$ and R8s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and d-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_110rcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, d-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
R98, R10s, R11s, R12s, R13s, R14s, R15s and R16s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, CδHs-heterocyclyl and C3-10-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyIf wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6-alkoxy, C2-C8-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2-, -NR225- and -CR22δH235-;and
wherein R228 and R238 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C8-alkoxy, C1-6-a'kenyl, aryl, heteroaryl, C1-6-heterocyclyl and dMo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci.6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-

e-alkyl, C1-6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyciyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nrtro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R58, R68, R7s and R88; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R98, R10s, R1ls, R12s, R13s, R14s, R15s, R16s, R18s. R19s, R206, R218, R228 and R238.
In one embodiment, the invention is concerned with compounds of the general formula XXI,
wherein E is selected from the group consisting of -O and -CR22δH238-.
In another embodiment, the invention is concerned with compounds of the general formula
XXI, wherein there are no covalent bonds between any of the substituents R5*, R68, R76 and
R88.
in another embodiment, the invention is concerned with compounds of the general formula
XXI, wherein R58, R6s, R7s and RBs are independently selected from the group consisting of
hydrogen, F, CI, C1-6-alkyl, C3-8-alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0-2-
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXI, wherein there is a covalent bond between R10s and R11s.
In another embodiment, the invention is concerned with compounds of the general formula
XXI, wherein there is a covalent bond between R13s and R228.
In another embodiment, the invention is concerned with compounds of the general formula
XXI, wherein R9s, R10s, R118, R12s, R13s, R14s, R15s and R16s are all hydrogen or F.
In an aspect of the invention, compounds are of the general formula XXII


wherein E is selected from the group consisting of -O-, -S-, -S(=0)-, -S(=0)r. -NR18t- and -CR18tR19t-; and
R41, R5t, R4t. R71, Rat, R91, R10t, R11t, R12t, R13t, R14t, R15t, R16t, R17t, R18t and R19t are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, nitro, Chalkyl, C3-8 alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, Ci*-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci.6-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenylt aryl, heteroaryl, C3-8-heterocyclyl, and C3-icrcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl,, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy, with the proviso that R4t and Ra are not both methyl; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4t, R10t, R11t, R12t, R13t, R14t, R15t, R16t, R17t,R18t and R19t.

In one embodiment, the invention is concerned with compounds of the general rormuia AAH,
wherein E is selected from the group consisting of -O, -S-, -S(=0)-, -S(=0)r and -CR18tR19t-.
In another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein R1Bt is hydrogen or F.
in another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein R10t, R12t, R4t and R4t are all hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein Rm, R7*, Rw and R91 are independently selected from the group consisting of
hydrogen, F, CI, C3-8-alkyl, C1-6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)r
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein there is a covalent bond between R11t and R13t.
In another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein there is a covalent bond between R13t and R19t.
In another embodiment, the invention is concerned with compounds of the general formula
XXII, wherein R10t, R11t, R12t, R13t, R14\ R15t, R16t and R17t are all hydrogen or F.

wherein R4u, R50, R6u, R7u, R6u, R9", R10u, R11u, R12u, R13u, R14u and R15u are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkoxy, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cyc!oalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3_8-heterocyciyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10-cycloalkyl may optionally be substituted with one or more

substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, C1-6-alkyl, C1a6-alkaxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-aikyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8 heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that R4u, R5u and R6u are not all hydrogen; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)r, -NR16u- and
-CR1BuR17u-;
wherein R1Su and R17u are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-nrcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1. e-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8Mo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, Cswrheterocyclyi, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4u, R5u and R6u; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R8u, R9u, R10u and R11u; and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R12u, R13u, R14u, R15u, R16u and R17u.
In one embodiment, the invention is concerned with compounds of the general formula XXIII, wherein E is selected from the group consisting of -O-, -S-, -S(=0)-l -S(=0)2- and -CR1BuR17u-. In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R17u is hydrogen or F.
In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein there are no covalent bonds between any of the substituents R8u, R9u, R10u and R11u.
In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R8u, R9", R10u and R11u are independently selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)r OH, hydroxy, amino and perhalomethyL
In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein there is a covalent bond between R12u land R13u.
In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R12u, R13u, R14u and R15u are all selected from the group consisting of hydrogen, F, methyl and Chalkyl.
In an aspect of the invention, compounds are of the general formula XXIVa-b


C1-6-alkylf C1-6-aIkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, Ca-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, C3-8alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3_icrcycioalkyl, perhalomethyl and perhalometboxy; with the proviso that none of the substituents R4v, R5v and R6* are benzothiazolyl or benzooxazolyl; and
E is selected from the group consisting of -0-, -S-, -S(=Oh -S(=0)r, -NR19v- and -CR19vR20v-; and
wherein R19v and R20* are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaIkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R7v and R8v or between the substituents R9v and R10v; and

wherein there may optionally be a covalent bond between R6v and a substituent selected from R8v and R9*; and
wherein there may be a covalent bond between any of the substituents selected from the group consisting of R4v, R5kand R6*; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R11v, R12v, R13v, R14v, R15v, R16v, R17v, R18v, R19v and R20*.
In one embodiment, the invention is concerned with compounds of the general formula XXIV, wherein E is selected from the group consisting of -0-, -S-, -$(=0)-, -S(=0)2- and -CR19vR20v-
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein R4t°v is hydrogen or F.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein there are no covalent bonds between any of the substituents R4v, R5kand R6v.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein there are no covalent bonds between any of the substituents R7v, R8v, R9v and
R10v.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein there are no covalent bonds between a substituent selected from the group
consisting of R4v, R5v and R6v and a substituent selected from the group consisting of R7v, R8v,
R9v and R10v.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein R7v, R8q, RSv and R10v are independently selected from the group consisting of
hydrogen, F, CI, d-ralkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)r
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein there is a covalent bond between R12v and R13v.
In another embodiment, the invention is concerned with compounds of the general formula
XXIV, wherein R11v, R12v, R13v, R14v, R15v, R16v, R17v and R18v are all hydrogen or F.
In an aspect of the invention, compounds are of the general formula XXV


wherein R4* Is selected from hydrogen, hydroxy, amino, sulfo, C3-8-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10rcycloalkyI, wherein each of hydroxy, amino, sulfo, C2-C8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3.1(rcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C41. 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyI, aryl, heteroaryl, C3_8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that R4w is not methyl, morpholine or a 2-chromen derivative; and
Z is selected from S, S(=0) and S(=0)2; and
R5", R6", R7w, R6w, R9w, R10w, R11w, R12w, R13w, R14w, R15w and R16w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl,heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8 heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8 alkyl, C1-6-alkoxyf C2.4ralkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8alkyl, perha-lomethyl and perhalomethoxy: and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)r, -NR17w- and -CR17wR18w-; and
wherein R17w and R18w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C3-8-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8alkoxy, C3-8-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci. wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4w, R5*, R6", R7w and RBw; and
wherein there may optionally be one or more covalent bonds between any of the substituents
selected from the group consisting of R9w, R10wt R11w, R12w, R13w, R14w, R15w, R1fiw, R17w and Riew
In one embodiment, the invention is concerned with compounds of the general formula XXV,
wherein the only substituents which are covalently bound are R4w and R5w.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein there are no covalent bonds between any of the substituents R5w, R6w, R7w and
R8W.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein there are no covalent bonds between any of the substituents R9", R10w, R11w,
R12w, R13w, R14w, R15w and R16w.

In another embodiment the invention is concerned with compounds of the general formula XXV, wherein E is selected from the group consisting of -0-, -S-, -S(=0)-f -S(=0)2- and -
CR17wR18w_
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein R1Bw is hydrogen or F.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein R5*, R6*, R7w and RBw are independently selected from the group consisting of
hydrogen, F, CI, C3-8alkyl, C3-8-alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein there is a covalent bond between R10w and R11w.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein there is a covalent bond between R13w and R17w.
In another embodiment, the invention is concerned with compounds of the general formula
XXV, wherein R9*, R10w, R11w, R12w, R13w, R14w, R15w and R16w are all hydrogen or F.
In an aspect of the invention, compounds are of the general formula XXVI

wherein R4xis selected from imino, C3-8-alkyl, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of imino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein

each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8alkyl, C1-6alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8alkyl, C3-8alkoxy, C2-C6-alkenyl, perhalomethyl and perhalomethoxy; and
R5", R6x, R7x, R5k, R9x, R10x, R11x, R12x and R13x are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-a!kenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-aikyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of-O-, -S-, -S(=0)-, -S(=0)2-, -NR14x- and -CR15xR16x-;
wherein R14x is selected from hydrogen, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8no-cycloalkyl, wherein each of sulfo, C3-8-alkyl. C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8crcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl. C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl,

heteroaryl, C3-8-heterocyclyI, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyana, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenylf aryl, heteroaryl, C3-8rheterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo, C1-ralkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclylt and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
R15x and R16x are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3_8-heterocyclyI and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-aIkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4x and R5x; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R6", R7x, R8q and R5k; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10x, R11x, R12x, R13x, R14x, R15x and R16x.
In one embodiment, the invention is concerned with compounds of the general formula XXVI, wherein R5k, R7x, R8x and R5k are independently selected from the group consisting of hydrogen, F, Ci, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2) -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment the invention is concerned with compounds of the general formula XXVI, wherein R10x, R1lxt R12x and R13x are independently selected from the group consisting

of hydrogen, F, CI, C1-6-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)δHNH2, -NH-S(=0)2-OH, hydroxy, amino and perhaiomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between the substituents R6x and R7x. In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between the substituents R10x and R11x. , In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between R10x and a substituent selected from R14x and R15x.
In an aspect of the invention, compounds are of the general formula XXVII

wherein R4y and R11y are independently selected from imino, C3-8-alkyl, C2-C6-alkenyl, aryl, het-eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of imino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C1-6-aIkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, C3-10-cycloalkylt wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,

amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8alkenyl, perhaiomethyl and perhalomethoxy; and
R5y, R6y, R7y, R4t*t R9y and R10y are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl,wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3*-heterocydyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1. 6-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C3-8-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, dwrheterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, d-a-heterocyclyl, C3-10-cycloalkyl, perhaiomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4y and R5y; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of RBy, R7y, R8y and R9y; and
wherein there may optionally be a covalent bond between the substituents R10y and R11y.
In one embodiment, the invention is concerned with compounds of the general formula XXVII, wherein R6y, R7y, R8y and R97 are independently selected from the group consisting of hydrogen, F, CI, C1-6-alkyl. C1-6-alkoxy, -C(=0}NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy, amino and perhaiomethyl.

In another embodiment, the invention is concerned with compounds of the general formula
XXVII, wherein there are no covalent bonds between any of the substituents R6y, R7y, R8y and
R9*.
In another embodiment, the invention is concerned with compounds of the general formula
XXVII, wherein there is a covalent bond between the substituents R4y and R5y
In another embodiment, the invention is concerned with compounds of the general formula
XXVIi, wherein there is a covalent bond between the substituents R10y and R11y.
In an aspect of the invention, compounds are of the general formula XXVIII

wherein R4z, R8z, R92, R10z, R11z. R12z, R13z, R14z, R15z, R16z and R17z are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyIf wherein each of , hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenylf aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8 alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C8-alkeny!, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3_B-heterocycIyI, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and

Rfe is a carbon bound substituent selected from C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2.r-alkenylI aryl, heteroaryl, C3-8-heterocyclyl, and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, dwr heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C1-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
Rte and R7z are independently selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and d-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C1-6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, d-a-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl. C1-6-alkoxy, dMs-alkenyl, aryl, heteroaryl, C:wrheterocyclyl, d_10-cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of -0-, -S-, -S(=Oy, -S(=0)z-, -NR18z- and -CR192R20z-;

wherein R18z is selected from hydrogen, sulfo, Chalkyl, C3-8alkenyl, aryl, heteroaryl, CM-heterocydyi and C3-10-cycloalkyl, wherein each of sulfo, C1-6-alkyl, C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Chalkyl, C3-8alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclylt C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
R1te and R202 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and Quo-cycloalkyl may op-tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaIkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4z and R5z; and
wherein there may optionally be a covalent bond between any of the substituents R7z, R8z, and R92; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10z, R112, R12z, R13z, R14z, R15z, R16z, R17z, R18z, R19z, and R20z.

In one embodiment, the invention is concerned with compounds of the genera! formula
XXVIII, wherein there is a covalent bond between the substituents R4z and R52.
In another embodiment, the invention is concerned with compounds of the general formula
XXVill, wherein R62, R7z, Rte and RδH are independently selected from the group consisting of
hydrogen, F, CI, Chalkyl, C1-6alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-
OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXVIII, wherein there is a covalent bond between R13z and a substituent selected from R182
and R19z.
In an aspect of the invention, compounds are of the general formula XXIX

wherein R4aa is selected from hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-C6-aIkenyI, aryl, heteroaryl; C3-8r heterocyclyi, and C3-10*cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, Cs-8-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxyt (δH-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, C3-10-cycloalkyl, perhalomethyl and perha-lomethoxy; and

R5aa peaaδH R7* pSaaδH RBΔH RlOaa- R11aa- R12aa apd R13aa afe independentJy selected from hydrogen, hydroxy, sulfanyi, sulfo, halogen, amino, cyano, nitro, Chalkyl, C3-8alkoxy, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyi, sulfo, amino, C1-6-alkyl, C3-8alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-aIkenyi, aryl, heteroaryl, C3-8-heterocyclyl, and C3.io-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C3-8alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyI, aryl, heteroaryl, CM-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3_10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R5aa and R6aa or between the substituent R7aaand R8aa; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R933, R10aa, R11aa and R12aa; and
E is selected from the group consisting of -0-, -S-, -S(=0)- and -S(=0)2-.
in one embodiment, the invention is concerned with compounds of the general formula XXIX, wherein there is a covalent bond between the substituents R9aa and R10aa. In another embodiment, the invention is concerned with compounds of the general formula XXIX, wherein R5sa, R6aa, R7aa and R833 are independently selected from the group consisting of hydrogen, F, CI, C3-8-alkyl,, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XXIX, wherein at least one of the substituents R5aa, R633, R7aa and R8aa are different from hydrogen.

In an aspect of the invention, compounds are of the general formula XXX

wherein R486 is selected from sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C8-alkenyl, aryl, heteroaryl, Cwrheterocyclyl, and C3,10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of -NR13ab- and -CR14abR15ab-; and
R5ab( R6ab( R7ab| R8ab( R9ab- R10abf R11ab- R12abj R13ab- R14ab and R15ab ape independently Selected
from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C1-6-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-

alkyl, C3-8-alkoxy, Cu-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, het-eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, (Wheterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R536 and R6315 or between the substituent R7ab and R8ab; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9ab, R10ab, R11ab, R12ab, R13ab, R14ab and R15ab.
In one embodiment, the invention is concerned with compounds of the general formula XXX, wherein there is a covalent bond between the substituents R9ab and R10ab. In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein there is a covalent bond between R10ab and a substituent selected from R13ab and R14ab.
In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein R535, R6ab, R7ab and R8ab are independently selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC=oy-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein at least one of the substituents R5ab, R6ab, R7ab and R8ab are different from hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein at least one of the substituents R9ab, R10ab, R11ab, R12ab, R13ab, R14ab and R15ab are different from hydrogen.
In an aspect of the invention, compounds are of the general formula XXXI


wherein R430 is a carbon bound substituent selected from C1-6-alkyl, C2-6-aIkenyl- aryl? heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and XC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocycIyl, C3-icrcycloalkyl, perhalomethyl and perha-lomethoxy; and
A1ac is N or C-R9ac; A3ac is N or C-R10ac; and A5ac is N or C-R11ac; and
R5ac, R630, R7ac, R830, R9ac, R10ac and R11ac are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3_10-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8alkoxy, C2-C6-aIkenyl; aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C1-6-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-

alkyl, C1-6-alkoxy, C2-B-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-6-alkyl, C1-6-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suifo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that A3ac is not C-C(OH)(CF3)2; and
A230 is N or OR1230; and A430 is N or C-R13ac; wherein
R12ac and R13ac are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkylf wherein each of sulfanyl, sulfo, amino, C3-8-alkyl,, C2_6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3_8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyctyl, and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, Ca-s-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycIoalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R4ac and a substituent selected from the group consisting of R5ac and R6ac; with the proviso that A1ac, A230, A3ac, A4ac and A530 are not all CH; and
wherein there may optionally be a covalent bond between any of the substituents R6ac, R7ac and R8ac; and
wherein there may optionally be one or more covalent bonds between any of the substituents in A1ac, A230, A330, A430 and A5ac.

In one embodiment, the invention is concerned with compounds of the general formula XXXI,
wherein there is a covalent bond between the substituents R430 and R6ac.
In another embodiment, the invention is concerned with compounds of the general formula
XXXI, wherein there is a covalent bond between A3ac and A430.
In another embodiment, the invention is concerned with compounds of the general formula
XXXI, wherein there is a covalent bond between A3ac and A280.
In another embodiment, the invention is concerned with compounds of the general formula
XXXI, wherein R530, R6ao, R7ac and R8ac are independently selected from the group consisting
of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-
S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula
XXXI, wherein at least one of the substituents A1ac, A280, A3ac, A430 and A5ac are different from
CH.
In an aspect of the invention, compounds are of the general formula XXXIIa-b

wherein R4*1 is selected from hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C3-8-alkyl, d-6-aIkoxy, C2-C6-aIkenyI, aryl, heteroaryl, C2-C8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently se-

lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha-lomethoxy, and
R5ad, R6ad, R7adf R8ad and R9ad are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8 heterocydyl and C3-10-cycballcy!, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C1-6-alkoxy, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8 e-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C1-6-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkaxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaIkyl, perhalomethyl and perha-lomethoxy; and
R10ad are selected from imino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkoxy, C3-8-alkenyl, aryl, heteroaryl, CM-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkoxy, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and

wherein there may optionally be a covalent bond between R4911 and a substituent selected from R8- and R7ad; and
wherein there may optionally be a covalent bond between the substituents R8q1 and R10ad so as to form a 5-membered ring system.
In one embodiment, the invention is concerned with compounds of the general formula XXXHa-b, wherein the substituents R9ad and R10ad are covalently bound so as to form a 5-membered ring system.
In another embodiment, the invention is concerned with compounds of the general formula XXXIla-b, wherein said 5-rnembered ring system comprises at least one nitrogen atom in the ring.
In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein said 5-membered ring system contains 5 carbons in the ring. In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein there is a covalent bond between the substituents R4t*d and R7ad. In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein R6"1, R6ad, R7ad and R8ad are independently selected from the group consisting of hydrogen, F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another aspect of the invention, compounds are of the general formula XXXIIIa-b

wherein E is selected from the group consisting of-O-, -S-, -S(=0)-, -S(=0)2-, -NR16ae- and -
CR17aeR18aes apd

p4ae p5ae p6ae p7ae pBae p9ae p10ae p11ae p12ae p13ae p14ae p15ae pIBae p17ae _nj pl8ae ---
independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, Cwrheterocyclyl and CsMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-er alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cv6-alkyl, C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyI, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between any of the substituents selected from R4*5, R536, R6ae and R7ae; with the proviso that when R5ae and R6ae are covalently bound they do not form a isoquinolin-3-yl or a substituted isoquinolin-3-yl together with the pyridine which they are both bound to; and
wherein there may optionally be a covalent bond between any of the substituents selected from R8ae, R9ae, R10ae, R11ae, R12ae, R13ae, R14ae, R15ae, R16ae, R17ae and R1Bae.
In one embodiment, the invention is concerned with compounds of the general formula
XXXIIIa-b, wherein there is a covalent bond between R6ae and R7ae.
In another embodiment, the invention is concerned with compounds of the general formula
XXXIIIa-b, wherein there is a covalent bond between R5ae and R6ae.
In another embodiment, the invention is concerned with compounds of the general formula
XXXIIIa-b, wherein at least one of R8ae, R9ae, R10ae, R11ae, R12ae, R13ae, R14ae and R15ae is se-

lected from F, CI, d-r-alkyl, C3-8-alkoxy, -C(=0)NH2l -NHCδHOMDH, -S(=0)2-NH2, -NH-S(=0-2-OH, hydroxy, amino and perhaiomethyl.
In another aspect of the invention, compounds are of the general formula XXXIV

wherein R4af, R5af, R6af, R7af, R8af, R9af, R10af, R11af, R12af, R13af, R14af and R15af are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2. 6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, Cswrheterocyclyl, C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, CiMralkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl, C3-8-io-cycloalkyl, perhaiomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R6af and any of the substituents selected from R5af and R7af; and

wherein there may optionally be a covalent bond between the substituents R9af and R10af; and
R18af is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8alkenyl, CM-heterocyciyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-C6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and per-halomethoxy; with the proviso that R16af is not methyl; and
wherein there may optionally be a covalent bond between the substituents R12af and R16af.
In one embodiment, the invention is concerned with compounds of the general formula XXXIV, wherein there is a covalent bond between the substituents R5af and R6af. In another embodiment, the invention is concerned with compounds of the general formula XXXIV, wherein there is a covalent bond between the substituents R9af and R1Qaf. In another embodiment, the invention is concerned with compounds of the general formula XXXIV, wherein at least one of R8af, R9af, R10af, R11af, R12af, R13af, R14af and R15af is selected from F, CI, C1-6-alkyl, C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=OVNH* -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another aspect of the invention, compounds are of the general formula XXXV


wherein E is selected from the group consisting of -O-, -S-, -S(=0)-, -S(=0)r and -
CR16agRl7ag_; and
R4", R5a9, R639, R10ag, R1139, R12as, R13a9f R16ag and R17ag are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-nrcycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cydoalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, « aryl, heteroaryl, C3-8-heterocyclyl, and C3.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R439 is not -CH2-N(CH3)2; and
wherein there may optionally be a covalent bond between the substituents R5ag and R639; and
R7ag is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, cyano, nitro, C3-8-alkyl, C2-C6-aikenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sul-

fanyl, sulfo, C1-6-aIkyI, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-icrcycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkylf wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, Cs-10-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-rheterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-C6-alkenylf aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_s-heterocyclyI, C3-10-cycloaIkyI, perhalomethyl and perhalomethoxy;
R8aa, R9ag, R14a9 and R15ag are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl,, C2-C6«alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycIoaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyI, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-

alkyl, C2-6-alkenyl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloaIkyl, perhalomethyl and perha-lomethoxy; and
wherein there may optionally be a covalent bond between the substituents R9ag and R10ag; and
wherein there may optionally be a covalent bond between the substituents R12ag and R16aB.
in one embodiment, the invention is concerned with compounds of the general formula XXXV, wherein there is a covalent bond between the substituents R5a9 and Rteg. In another embodiment, the invention is concerned with compounds of the general formula XXXV, wherein there is a covalent bond between the substituents R989 and R10ag. In another embodiment, the invention is concerned with compounds of the general formula XXXV, wherein at least one of R8ag, R9ag, R10a9, R11ag, R12aB, R13ag, R14ag and R15ag are selected from F, CI, C3-8alkyt, C1-6alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.

wherein R43*, R5ah, R6ah, R7ah, R8ah and R9ah are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-aikenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl,, C2-C6-aIkenyi, aryl, heteroaryl, C3-8-heterocycIyl, and C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted

with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, Ca.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-6-alkenyI, aryl, heteroaryl, (Wheterocyclyl and Cs-jo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C2-C8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R5ah and R6ah are not both CF3; and
wherein there may optionally be a covalent bond between any of the substituents selected from K4* R5ah, R6ah and R7ah; and
wherein there may optionally be a covalent bond between the substituents R8ah and R9ah; with the proviso that when R8δH and R9ah together with the carbon to which they are bound forms phenyl then R5ah, R6ah, R7ah and R8ah are not all hydrogen.
In one embodiment, the invention is concerned with compounds of the general formula
XXXVIa-b, wherein there is a covalent bond between RBah and R9aIn another embodiment, the invention is concerned with compounds of the general formula
XXXVla-b, wherein there is a covalent bond between R6ah and R7ah.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVla-b, wherein there is a covalent bond between R5ah and R8q.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVIa-b, wherein at least one of R5ah, R6ah, R7ah and R8ah are selected from F, CI, C1-6-alkyl,
Cve-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-OH, hydroxy, amino and
perhalomethyl.
In another aspect of the invention, compounds are of the general formula XXXVII


R4al, R5al, R6*, R7ai, R8ai and R931 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C-Mo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3.io-cycloalkyl, perhalomethyl and per-halomethoxy; with the proviso that R4ai is not CH2-N(Me)2; and
wherein there may optionally be a covalent bond between any of the substituents selected from R4*, R5ai, R6ai and R7ai; and
wherein there may optionally be a covalent bond between the substituents R8al and R9*; with the proviso that RBai and R9ai together with the carbon to which they are bound do not form 4-methoxy-phenyl, 4-chlon-phenyl or4-nitro-phenyl.

In one embodiment, the invention is concerned with compounds of the general formula
XXXVII, wherein there is a covalent bond between RBai and R9ai.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVII, wherein there is a covalent bond between R6ai and R7ai.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVII, wherein there is a covalent bond between R5aI and R6ai.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVII, wherein at least one of R5*, R6*, R7ai and RBai are selected from F, CI, C3-8-alkyl, C3-8-
alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and per-
halomethyl.
In another aspect of the invention, compounds are of the general formula XXXVIII

wherein R48*, R53', R6aJ and R7ai are independently selected from amino, cyano, nitro, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-icrcycloalkyl, wherein each of amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy* sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substftuents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino,

cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covaient bond between the substituents R43' and R531; and
wherein there may optionally be a covaient bond between the substituents R63' and R7aJ.
In one embodiment, the invention is concerned with compounds of the general formula
XXXVIII, wherein there is a covaient bond between R6aj and R7aj.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVIII, wherein R6aJ, R7aj and said covaient bond are selected so as to form a ring system
selected from an optionally substituted piperedine, piperazine, morpholine and thiomor-
pholine.
In another embodiment, the invention is concerned with compounds of the general formula
XXXVIII, wherein said ring system is selected from piperedine, piperazine, morpholine and
thiomorpholine
In another embodiment, the invention is concerned with compounds of the general formula
XXXVIII, wherein there is a covaient bond between R4aj and R5aj.
In another aspect of the invention, compounds are of the general formula XXXIX

wherein R43*, R53*, R63* and R7ak are independently selected from amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of amino, C3-8alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_i
halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, CsMo-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C1-6-alkyl, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-6-alkenyI, aryl, heteroaryl, CWheterocycIyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyi, amino, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, d-6-aIkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that none of R5kand R5ak are -C(=0)-0-isopropyl; and
wherein there may optionally be a covalent bond between the substituents R4δH and R5ak; with the proviso that R4a\ R5ak and the nitrogen to which they are bound do not form a substituted tetrazolyl moiety; and
wherein there may optionally be a covalent bond between the substituents R6ak and R7ak;
In one embodiment, the invention is concerned with compounds of the general formula
XXXIX, wherein there is a covalent bond between R6ak and R7ak.
In another embodiment, the invention is concerned with compounds of the general formula
XXXIX, wherein R6ak, R7ak and said covalent bond are selected so as to form a ring system
selected from an optionally substituted piperedine, piperazine, morpholine and thiomor- •
pholine.
In another embodiment, the invention is concerned with compounds of the general formula
XXXIX, wherein said ring system is selected from piperedine, piperazine, morpholine and
thiomorpholine
In another embodiment, the invention is concerned with compounds of the general formula
XXXIX, wherein there is a covalent bond between R4ak and R5ak.
In another aspect of the invention, compounds are of the general formula XXXX


wherein R43' and R531 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8lky!, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2„6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R4a) and R5al; with the proviso that R431 and R53' together with the nitrogen to which they are bound do not form 2,5-pyrrolidinedione or an annealed ring system comprising 3 or more rings; and
wherein E is selected from the group consisting of -0-, -S-, -S(=Oh -S(=0)2- and -NR14aI-, _CRi5aiRi6ai_; and
R63', R7al, RBaI, R9aI, R10al, R11aI, R12aI, R13aI, R14al, R15aI and R16al are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl,

aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-r-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and QMo-cycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci.6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyi, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and C3-to-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl,, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, Ca-B-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R7al and R8al; and
wherein there may optionally be a covalent bond between the substituents R10a! and a sub-stituent selected from R14al and R15al.
In one embodiment, the invention is concerned with compounds of the general formula
XXXX, wherein there is a covalent bond between the substituents R4ai and R531.
In another embodiment, the invention is concerned with compounds of the general formula
XXXX, wherein there is a covalent bond between the substituents R7al and RBal.
In another embodiment, the invention is concerned with compounds of the general formula
XXXX, wherein there is a covalent bond between R10al and a substituent selected from R14al
or R15al.

In another embodiment the invention is concerned with compounds of the general formula XXXX, wherein E is -NR14aI-.
In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R14al is selected from F, CI, C1-6-alkyl, C3-8alkoxy, -C(=0)NH2) -NHC(=0)-OH, i -S(=0)2-NH2, -NH-S(=0)rOH- hydroxy, amino and perhalomethyl.
In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein E is -CR15a,R16aI-.
In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R16al is selected from F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl. In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R15aI is hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein at least one of R6*, R7al, R8al, R9aI, R10al, R11al, R12al and R13aI are selected from F, CI, C3-8alkyl, C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2) -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.


wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C1-6-alkenyIF aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cydoalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl,C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyI, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-10-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3.1crcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, Cv,0-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R17am and R20am are not both hydroxy; and
wherein there may optionally be a covalent bond between R18am and a substituent selected from R17am and R19am; and
wherein there may optionally be a covalent bond between the substituents R10am and a substituent selected from R14am and R15am; and
wherein there may optionally be a covalent bond between the substituents R7am and R8am.
In one embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein there is a covalent bond between R1Bam and a substituents selected from R17am and R19am.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein there is a covalent bond between R10am and a substituent selected from
In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein E is -NR14am-.
In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein RiAam is selected from F, CI, C3-8-alkyl. C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-SδHOJjr-OH, hydroxy, amino and perhalomethyl. In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein E is -CR15amR16am-. .
In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein R16am is selected from F, a, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl. In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein R15am is hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein there is a covalent bond between R15am and R16am. In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein at least one of R6am, R7am, R8am, R9am, R10an\ R11am, R12am and R13am are selected from F, CI, d-6-alkyl. C3-8alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2t -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another aspect of the invention, compounds are of the general formula XXXXI I




In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein there is a covalent bond between the substituents R7an and R8an. In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein there is a covalent bond between R13an and a substituents selected from R17an and R1Ban.
In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein E is -NR17an-.
In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein E is -CR18anR19aIn another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein R19an is selected from F, CI, C3-8-alkyl, C3-8-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, «NH-S(=0)2-OHI hydroxy, amino and perhalomethyl. In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein R1fian is hydrogen.
In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein at least one of R53", R6an, R7an, R8an, R9an, R1Dan, R11an, R12an, R13an, R14an, R15an and R16an are selected from F, CI, C3-8-alkyl, Ci.6-alkoxy, -C(=0)NH2, -NHC(=0)-OH,-S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
In another aspect of the invention, compounds are of the general formula XXXXIII

wherein R4ao is selected from hydrogen, hydroxy, sulfo, halogen, amino, cyano, nitro, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and Cs-urcycloalkyl, wherein each of hydroxy, sulfo, amino, Chalkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy-

droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, aryl, het-eroaryl, C3-rheterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8alkyl, C2-C6-aIkenyt, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyIf aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenylf aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl,, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R5a0, R6ao, R7ao, Rte0, R9a0, R10a0, R11a0 and R12aD are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, dwrheterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocycly! and dMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-hetenocyclyl and CMo-cyctaalky! may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8rheterocyclyl and di-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C2-6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3. 10-cycloalkyl may optionally be substituted with one or more substituents independently se-

lected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-a!kenyl, pertialomethyl and perhalomethoxy;
with the proviso that any one of R6ao and R8ao is not methyl; and with the further proviso that R480, R580, R680, R7ao and R8ao are not all hydrogen; and
wherein there may optionally be a covalent bond beween R4a0 and R6ao; and wherein there may optionally be a covalent bond between R7ao and R8ao; and wherein there may optionally be a covalent bond between R9aD and R10ao.
In one embodiment the invention is concerned with compounds of the general formula
XXXXIII, wherein R530, R680, R7a0 and R8ao are independently selected from hydrogen and
fluor.
In another embodiment the invention is concerned with compounds of the general formula
XXXXIII, wherein R980, R10ao, R11ao and R12a0 are independently selected from hydrogen and
fluor.

wherein R1ap and R28* are independently selected from C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclylf and -cycloalkyl, wherein each of C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl,alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, nitro, C3-8-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycioalkyl, wherein each of hydroxy,

suifanyl, sulfo, amino, Chalky), C3-8-alkenyl, aryi, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and CWcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C8-alkenyl, perhalomethyl and perhalomethoxy, with the proviso that if R1ap and R2δH are identical then they are not methyl or ethyl; and
wherein there may optionally be a covalent bond between the substituents R1ap and R23*5; and
wherein R53*, R6ap and R7ap are independently selected from hydrogen and F; and
wherein R4ap is selected from hydrogen, hydroxy, suifanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl, and C3-10-cycloalkyl, wherein .each of hydroxy, suifanyl, sulfo, amino, C3-8-alkyl, Qws-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3.io-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C3-8-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-C6-alkenyls aryl, heteroaryl, C3-8-

heterocyclyl and CsMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; with the proviso that R4δH is not methyl.
In one embodiment the invention is concerned with compounds of the general formulae XXXXIVa-b, wherein R1ap and R5kkare not identical.
In another aspect of the invention, compounds are of the general formulae XXXXVa-b

wherein R1aq and R2aq are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-ralkenyl( aryl, heteroaryl, CM-heterocyclyI and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-8to-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, (Wheterocyclyl and C3.

lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, amino, C1-6-alkyl. C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy-droxy, suifanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl. C3-8-alkenyl, perha-iomethyl and perhalomethoxy; with the proviso that R1aq and R2r* are not both methyl; and
wherein there may optionally be a covaient bond between R1aq and R2r*; and
wherein R39*, R4δH, R5**, R69", R7aq, R8aq, R9aq, R10aq and R11a0 are indenpendently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, dwrheterocyclyl and C3-10-cycloa(kyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C1-6-heterocyclyl and C3-10-cycloalkyl rnay optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2_6-alkenyl- aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covaient bond between R4t*q and R53*; and

wherein R3aq is selected from the group consisting of -C(=0)-, -C(=0)NH-, -CH2-, -CH2CH2-, -CHF-, -CH2CHF-, -CHFCHr, -NH-, -S(=0)2-NH-, -NH-S(=0)r, -NHC(=Oh -0-, -S-, -S(=0)-, -S(=0)r; and
wherein there may optionally be a covalent bond between two substituents selected from
R8aq- R9aqj R10aq and R11ao
In one embodiment the invention is concerned with compounds of the general formulae XXXXVa-b, wherein there is one covalent bond between the substituents R1aq and R2δH. in another embodiment the invention is concerned with compounds of the general formulae XXXXVa-b, wherein R48", R5*1, R6aq and R7aq are independently selected from hydrogen and fluor.
In another embodiment the invention is concerned with compounds of the general formula XXXXVa-b, wherein R8"" is selected from -0-, -S-, -CHr, -CH2CH2-, -NH-, -NH-C(=0)-, -C(=0)-NH-, -S(=0)2-NH- and -NH-S(=0)2-.
In another aspect of the invention, compounds are of the general formula XXXXVI

wherein A1ar is N or C-R10ar; and A2*' is N or C-R11ar; and A3ar is N or C-R12ar; and
wherein R1ar, R2", R3ar, R43', R5ar, R6ar, R7arf R6ar, R9ar, R10ar, R11ar and R12ar are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloaIkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl,

sulfo, amino, C3-8-alkyl, C2-C6-alkenylI aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-C6-alkenyI, aryl, heteroaryl,heterocyclyl and C3-10-cycloaIkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, heterocyclyl and C3-10-cycIoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.1crcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-C6-alkenyl, perhalornethyl and perhalomethoxy; with the proviso that if R1ar and R281* are identical then they are not methyl or ethyl; and
wherein there may optionally be a covalent bond between R1ar and R231*.
In one embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein R9ar is S(=0)2-R13ar or C(=0)-R13ar; and wherein R13ar is selected from hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-Krcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6~aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and CcMo-cycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl. C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocycly! and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyi and C3-10-cycloaIkyl

may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, alkenyl, perha-lomethyl and perhalomethoxy
In another embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein R1ar and R23' are not identical.
In another embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein there is a covalent bond between the substituents R1ar and R2r.
In another aspect of the invention, compounds are of the general formula XXXXVII

wherein R1as, R238, R3as, R438, R5as, R6as, R7as, RBas and R9as are independetly selected from hydrogen and fluon and
wherein R10as is selected from aryl and heteroaryl, which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-aIkenyI, aryl, heteroaryl, CM-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo,

amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl( C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R12as is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, cyano, C1-6-alkyl, C2. 6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenylf aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8aHcyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-s-heterocydyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2.s-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloa!kyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3. 10-cycioalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R13as, R14as, R15as and R16as are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, CM-heterocyclyl, and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or

more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-6-heterocyclyl andC3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1(rcycIoalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, n'rtro, C3-8-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl .may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6alkenyl, perha-lomethyl and perhalomethoxy; with the proviso that R12as, R13as, R14as, R15as and R16as are not all hydrogen; and
wherein there may optionally be a covalent bond between the substituents R13as and R14as.
In one embodiment the invention is concerned with compounds of the general formula XXXXVII, wherein R13as, R14as, R15as and R16as are independently selected from hydrogen and fluor.

wherein R5*, R6at, R7at R8q, R9at, R10at R11at, R12at, R13at R14at, R15at, R16at, R17at and R18at are independently selected from hydrogen and fluor; and
wherein R431 is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycIoalkyl, wherein each

of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8B-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-aIkenyl, aryl, heteroaryl, Cwrheterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8alkyl, C2-C8-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cwrheterocyclyl and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R19at is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano e-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-10-cydoaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyI and C3-10-cycloalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyI may op-

tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, fluor, iodine, amino, cyano, nitro, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclyI and C3-10-cycloalkyl; with the proviso that R19at is not methoxy.
In one embodiment the invention is concerned with compounds of the general formula XXXXVIH, wherein R5at, R6at, R7at R8at, R9at, R1Dat R11at, R12at, R13at R14at, R15at( R16at, R17at and R18at are all hydrogen.
In another embodiment the invention is concerned with compounds of the general formula XXXXVIH, wherein R4at is an optionally substituted aryl or heteroaryl.
In another embodiment, the invention is concerned with compounds of the general formulae l-XXXXVIII, wherein said compound comprises only one F.
In another embodiment, the invention is concerned with compounds of the general formulae IrXXXXVIII, wherein said compound comprises two F and preferably three F. In another embodiment, the invention is concerned with compounds of the general formulae l-XXXXVIII.wherein said compound comprises a CF3 moiety.
In another embodiment, the invention is concerned with compounds of the general formulae . I-XXXXVIII, wherein said compound comprises a hydrophilic substituent selected from the group consisting of hydroxy, amino, C1-6-alkaxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NHS(=0)2-OH, -NHC(=0)-R1am, -NHS(=0)z-R1am, -NCRδHC3-8OJ-R23"1, -N(R1am)S(=0)2-R2am, wherein R1am and R23™ are independently selected from C3-8-alkyl. In another embodiment, the invention is concerned with compounds of the general formulae l-XXXXVIII, wherein said compound comprises a moiety selected from the group consisting of
-Examples of specific compounds of the invention are :































































able at least 10 mg/L, more preferable at least 50 mg/L and most preferable at least 200
mg/L as determined at 25 °C and pH 2.0.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which have an IC50 value of no greater than 5μm as determined by the assay 3190.2 or
3180.1 disclosed herein.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which have an IC50 value of less than 1 μM- preferably less than 500 nM, preferably less than
100 nM, preferably less than 50 nM, more preferable less than 25 nM, more preferable less
than 10nM and even more preferable less than 5 nM as determined by the assay 3190.2 or
3180.1 disclosed herein.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which are ionized at pH 7.0.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which have a pKa in the range from 8 to 12, preferable from 9 to 12, more preferable from 10
to 12.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which have a molar weight of no greater than 1000 D.
In another embodiment, the invention is concerned with compounds of formulae l-XXXXVIII,
which have a molar weight of less than 750 D, preferably less than 500 D, more preferable
less than 400 D, more preferable less than 300D and even more preferably less than 250 D.
In another aspect the present invention relates to the use of a compound of the general formula I

wherein R1 is selected from hydrogen, C1-6-alkyl, C2-C8-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxof halogen, amino, cyano and nitro; and
R2 is selected from C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independ-

ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C2„6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
X is O or S; and
L is a group such that -C(=X)-L is a hydrolysable group; or
a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs
for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, dia-cylglycerols, cholesterol acyl esters or steroid acyl esters.
Another aspect of the invention relates to use of a compound of the general formula I


wherein R1 is selected from hydrogen, C3-8-alkyl,, C2-C8-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and
R2 is selected from C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro,C1-6 -alkyl, C2-C6-aikenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkylf C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl,, C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
X is O or S; and
L is a group such that -C(=X)-L is a hydrolysable group; or

a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs
for the preparation of a medicament for the treatment of any disorder where it is desirable to
modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-choIesteroI, insulin and/or glucose; and/or
modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatide acids, long chain acyl-CoA's as well as citrate or malonyl-CoA; and/or
increase insulin sensitivity in adipose tissue, skeletal muscle, iiver or pancreatic p cells; and/or
modulate insulin secretion from pancreatic p cells.
Another aspect of the invention is the use of a compound of the general formula I for the preparation of a pharmaceutical medicament.
In one embodiment the present invention relates to the use of a compound of the general formula (I) for the preparation of a medicament for the treatment of insulin resistance, diabetes type 1, diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.
Another aspect of the invention is pharmaceutical compositions comprising a compound of formula I


wherein R1 is selected from hydrogen, C3-8-aikyl, C2-6-alkenyi and C3-10-cycloalkyI, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and
R2 is selected from C1-6-alkyI, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8alkyi, C2-6-alkenyl, aryl, heteroaryl, (Wheterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalkyl, C3-8alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl,, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
X is O or S; and
L is a group such that -C(=X)-L is a hydrolysable group; or
a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs.

In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein X is O. In another embodiment, the invention is concerned with pharmaceutical compositions comprising a compound of formula (I) and uses of the compounds of formula (I), wherein X is O. In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains an O, via which L is bound to the C in formula (I). In another embodiment, the invention is concerned with pharmaceutical compositions comprising a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains an O, via which L is bound to the C in formula (I). In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains a N, via which L is bound to the C in formula (I). In another embodiment, the invention is concerned with pharmaceutical compositions comprising a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains a N, via which L is bound to the C in formula (I).
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is selected from the group consisting of






wherein Y is O or S; and
Ra\ Ra2, Ra3, R34, R35 and Ra6 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, Cwrheterocyciyl, or C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-r-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl,

wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C2-6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C3-8aikenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (l), wherein at least one of Ra\ R32, R4t3, R34, Ra5 and Ra6 is F.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted -O-phenyl, via which L is bound to the C in formula (I). In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R1 and R2 are covalently bound to each other so that the group R1-N-R2 forms a piperazine, said pi-parazine being bound to the C in formula (I).
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R1 and R2 are covalently bound to each other so that the group R1-N-R2 forms a piperedine, said piperidine being bound to the C in fornula (I).
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (l), wherein R1 is selected from the group consisting of C3-8-alkyl, C2_6-aIkenyl and C3-10-cyc!oalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro.

In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (1) and uses of the compounds of formula (1), wherein R1 is methyl.
In yet another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R1 is phenyl.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R2 is a heteroaryl.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R1 is methyl and R2 is phenyl.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted -O-phenyl via which L is bound to the C in formula (I), and R1 and R2 are covalently bound to each other so that the group R1-N-R2 forms a pipa-razine, said piparazine being bound to the C in fomula (I).
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted -O-phenyl via which L is bound to the C in formula (I), and R1 and R2 are covalently bound to each other so that the group R1-N-R2 forms a piperedine, said piperedine being bound to the C in fomula (I).
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted -O-phenyl via which L is bound to the C in formula (I), and R1 is methyl and R2 is phenyl.
In another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein pKa of the group L is between 4 and 12, between 6 and 12, between 7 and 12, between 8 and 12, preferably between 8.5 to 11.5, and most preferable between 9.0 to 11.0. In another embodiment, the invention is concerned with pharmaceutical compositions containing the compounds of formula (I) and uses of the compounds of formula (I), wherein administration of said compound is by oral administration

In another embodiment, the invention is concerned with pharmaceutical compositions containing the compounds of formula (!) and uses of the compounds of formula (1), the nasal, transdermal, pulmonal, or parenteral route.
Another aspect of the invention is a method of treating any disorder where it is desirable to inhibit the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglyc-erols, cholesterol acyl esters or steroid acyl esters, wherein said method comprises the use as described above.
In another embodiment, the invention is concerned with a method of treating any disorder where it is desirable to modulate the plasma level of free fatty acids or to modulate the handling, storage and oxidation of intracellular fatty acid and cholesterol, wherein said method comprises the use as described above.
In another embodiment, the invention is concerned with said method, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1, diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.


In another embodiment, the invention is concerned with the process of scheme Plf wherein said solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide and N-methyipyrolidone.
In another embodiment, the invention is concerned with the process of scheme Pi, wherein said base is selected from the group consisting of triethylamine, N,N-diisopropyl-N-ethylamine and DABCO.
In another aspect the invention is concerned with a process for the preparation of a compound according to the general formula

wherein R1 is selected from C3-8-alkyl, C2-C6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sul-fanyl, oxo. halogen, amino, cyano and nitro; and
R2 is selected from C3-8-alkyl, C2-C6-alkenyt, aryl, heteroaryl,C3-8heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl,, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-10-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more

substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
R3 is selected from hydroxy, sulfanyl, sulfo, amino, C3-8alkyl, C3-8-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yI and C3-10-cycloaIkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C6-alkenylf aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-C8-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C3-8-alkyl, C2-C8-aIkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycioalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C3-8-alkyl, C3-8-alkenyl, perhalomethyl and perhalomethoxy; and
X is O or S; or
a compound according to any one of formulae lll-XXXXVIII; or
a pharmaceutically acceptable salt thereof;
said process comprising the treatment of the appropriate amine, R1-NH-R2, with the appropriate acylating reagent, Y-C(=X)-R3, in a solvent and in the presence of a base according to the reaction scheme P2


In one embodiment, the invention is concerned with the process of scheme P2, wherein Y is CI.
In another embodiment, the invention is concerned with the process of scheme P2f wherein R3 is an aryloxy group.
In another embodiment, the invention is concerned with the process of scheme PδH wherein said solvent is selected from the group consisting of diethyl ether, tetrahydrofuran and di-chloromethane.
In another embodiment, the invention is concerned with the process of scheme P2) wherein said base is selected from the group consisting of trimethylamine, triethylamine, ethyl-diisopropyl-amine and 1,4-diazabicyclo[2.2.2]octane.
In another embodiment, the invention is concerned with the process of scheme P2, wherein said base is present as a functionality in one or both of the substituents R1 and R2, thus forming a salt with the acid H-Y.
In another aspect the invention is concerned with a pharmaceutical composition comprising a compound of formulae l-XXXXVIIl or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
In one embodiment the invention is concerned with a pharmaceutical composition, wherein said composition is in unit dosage form, comprising from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of a compound of formulae l-XXXXVIIl or a pharmaceutically acceptable salt thereof. In another embodiment the invention is concerned with a pharmaceutical composition for use as a medicament for inhibiting the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters, said composition comprising a compound of any one of formulae l-XXXXVIIl or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
In another embodiment the invention is concerned with a pharmaceutical composition for oral, nasal, transdermal, puimonal, or parenteral administration.

In another aspect the invention is concerned with use of a compound according to any one of formulae l-XXXXVIII for preparation of a medicament for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters.
In one embodiment the invention is concerned with said use, wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is used.
In another aspect the invention is concerned with use of a compound according to any one of formulae l-XXXXVIII for the preparation of a medicament for the treatment of any disorder where it is desirable to
modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, insulin and/or glucose; and/or
modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatide acids, long chain acyl-CoA's as well as citrate or malonyl-CoA; and/or
increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic p cells; and/or
modulate insulin secretion from pancreatic (3 cells.
In one embodiment the invention is concerned with said use, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1 and 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.
In another aspect the invention is concerned with use of a compound according to any one of formulae l-XXXXVIII or a pharmaceutically acceptable salt thereof for the preparation of a medicament.
In another aspect the invention is concerned with a method of treating a disorder of a patient where modulation of the activity of hormone-sensitive lipase is desired, the method

comprising administering to said patient an effective amount of a compound according to any one of formulae I-XXXXVIH or a pharmaceutically acceptable salt thereof. In one embodiment the invention is concerned with said method, wherein said administration is carried out by the oral, nasal, transdermal, pulmonal, or parenteral route. In another embodiment the invention is concerned with said method, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1 and 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.
In another embodiment the invention is concerned with said method, wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is administered to the patient
The present invention also encompasses pharmaceutically acceptable salts of the present compounds. Such salts include pharmaceutically acceptable acid addition salts, pharmaceu-tically acceptable base addition salts, pharmaceutically acceptable metal salts, ammonium and alkylated ammonium salts. Acid addition salts include salts of inorganic acids as well as organic acids. Representative examples of suitable inorganic acids include hydrochloric, hy-drobromic, hydroiodic, phosphoric, sulfuric, nitric acids and the like. Representative examples of suitable organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, glycolic, lactic, maleic, malic, malonic, mandelic, oxalic, picric, pyruvic, salicylic, succinic, methanesulfonic, ethanesulfonic, tartaric, ascorbic, pamoic, bismethylene salicylic, ethanedisulfonic, gluconic, citraconic, aspartic, stearic, palmitic, EDTA, glycolic, p-aminobenzoic, glutamic, benzenesulfonic, p-toluenesulfonic acids, sulphates, nitrates, phosphates, perchlorates, borates, acetates, benzoates, hydroxynaphtho-ates, glycerophosphates, ketoglutarates and the like. Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci. 1977,66, 2, which is incorporated herein by reference. Examples of metal salts include lithium, sodium, potassium, magnesium, zinc, calcium salts and the like. Examples of amines and organic amines include ammonium, methylamine, di-methylamine, trimethylamine, ethylamine, diethylamine, propylamine, butylamine, tetrame-thylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, choline, NδH'-dibenzylethylenediamine, N-benzylphenylethylamine, N-methyl-D-glucamine, guanidine and the like. Examples of cationic amino acids include lysine, arginine, histidine and the like.

The pharmaceutically acceptable salts are prepared by reacting the compound of formulae I-XXXXVIII with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, THF, methanol, t-butanol, dioxane, isopropanol, ethanol etc. Mixture of solvents may be used. Organic bases like lysine, arginine, diethanolamine, choline, guandine and their derivatives etc. may also be used. Alternatively, acid addition salts wherever applicable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric add, phosphoric acid, p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc. Mixture of solvents may also be used.
The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, enzymatic resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as brucine, (/?)- or (S)-phenylethylamine, cinchona alkaloids and their derivatives and the like. Commonly used methods are compiled by Jaques et al in "Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981). More specifically the compound of formula I may be converted to a 1:1 mixture of diastereomeric amides by treating with chiral amines, aminoacids, aminoalcohols derived from aminoacids; conventional reaction conditions may be employed to convert acid , into an amide; the dia-stereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formulae l-XXXXVIII may be prepared by hydrolysing the pure diastereomeric amide.
Various polymorphs of compound of general formulae I-XXXXVHI forming part of this invention may be prepared by crystallization of compound of formulae l-XXXXVIll under different conditions. For example, using different solvents commonly used or their mixtures for recrys-tallization; crystallizations at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques.

The invention also encompasses prodrugs of the present compounds, which on administration undergo chemical conversion by metabolic processes before becoming active pharmacological substances. In general, such prodrugs will be functional derivatives of the present compounds, which are readily convertible in vivo into the required compound of the formulae l-XXXXVIII. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.
The invention also encompasses active metabolites of the present compounds. The invention also relates to pharmaceutical compositions comprising, as an active ingredient, at least one compound of the formula I or any optical or geometric isomer or tautomeric form thereof including mixtures of these or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers or diluents. Furthermore, the invention relates to the use of compounds of the general formulae I-XXXXVIII or their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof for the preparation of a pharmaceutical composition for the treatment and/or prevention of disorders where a decreased level of plasma FFA is desirable, such as the conditions mentioned above. In another aspect, the present invention relates to a method of treating and/or preventing type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.
In a still further aspect, the present invention relates to the use of one or more compounds of the general formulae l-XXXXVIII, or pharmaceutically acceptable salts thereof, for the preparation of a pharmaceutical composition for the treatment and/or prevention of type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.
In a still further aspect, the present compounds are useful for the delaying or prevention of the progression from impaired glucose tolerance to type 2 diabetes. In a still further aspect, the present compounds are useful for the delaying or prevention of the progression from non-insulin requiring type 2 diabetes to insulin requiring type 2 diabe tes.
In another aspect, the present compounds reduce triglyceride levels and are accordingly useful for the treatment and/or prevention of ailments and disorders such as diabetes and/or obesity.
In still another aspect, the compounds of general formulae l-XXXXVIII are useful for the treatment of hyperglycemia, elevated HbAic level, hyperinsulinemia, type 1.5 diabetes, latent

autoimmune diabetes in adults, maturity onset diabetes, beta-cell apoptosis, hemochromatosis induced diabetes, impaired glucose tolerance, impaired fasting glucose, metabolic syndrome X, insulin resistance, impaired lipid tolerance, cystic fibrosis related diabetes, polycystic ovarian syndrome, and gestational diabetes.
In still another aspect, the compounds of general formulae l-XXXXVIII are useful for the treatment of obesity, dyslipidemia, diabetic dyslipidemia, hyperlipidemia, hypertriglyceridemia, hyperlipoproteinemia, hypercholesterolemia, hypertension, essential hypertension, acute hypertensive emergency, arteriosclerosis, atherosclerosis, restenosis, intermittent claudication (atherosclerosis oblitterens), cardiovascular disease, cardiomyopathy, cardiac hypertrophy, left ventricular hypertrophy, coronary artery disease, early coronary artery disease, heart insufficiency, exercise tolerance, chronic heart failure, mild chronic heart failure, arrhythmia, cardiac dysrythmia, syncopy, heart attack, myocardial infarction, Q-wave myocardial infarction, stroke, acute coronary syndrome, angina pectoris, unstable angina, cardiac bypass reocclusion, diastolic dysfunction, systolic dysfunction, non-Q-wave cardiac necrosis, catabolic changes after surgery, acute pancreatitis, and irritable bowel syndrome
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the treatment of diabetic retinopathy, background retinopathy, preproliferative retinopathy, proliferative retinopathy, macular edema, cataracts, nephropathy, nephrotic syndrome, diabetic nephropathy, microalbuminuria, macroalbuminuria, neuropathy, diabetic neuropathy, distal symmetrical sensorimotor polyneuropathy, and diabetic autonomic neuropathy.
In still another aspect, the compounds of general formulae l-XXXXVIII are useful for increasing the number of beta-cells in a patient, increasing the size of beta-cells in a patient or stimulating beta-eel! proliferation, modulating beta-cell function and insulin secretion in a patient in need thereof, which method comprises administration of an effective amount of a compound of formulae l-XXXXVIII to a patient in need thereof.
The compounds of the invention are also believed to be useful for reducing body weight in a patient in need thereof.
The compounds of the invention are also believed to be useful Use for weight neutral treatment of above mentioned diseases.
The compounds of the invention are also believed to be useful for redistributing fat in a patient in need thereof.

The compounds of the invention are also believed to be useful for redistributing central fat in a patient in need thereof.
The compounds of the invention are also believed to be useful for reducing or preventing central obesity.
The compounds of the invention are also believed to be useful for reducing postprandial serum lipid excursions.
The compounds of the invention are also believed to be useful for the treatment of fatty acid oxidation disorders such as MCAD.
In still another aspect, the compounds of general formulae l-XXXXVIII are believed to be useful for the treatment of a disease, condition or disorder wherein cholesterol is a precursor. Such diseases, conditions or disorders may relate to testosterone, e.g. male contraception, excessive testosterone levels, PCOS and prostate cancer. They may also relate to Cortisol or corticotropin, e.g. Cushing disease.
The compounds of the invention are also believed to be useful for the treatment of cancer. Thus, the compounds of the general formulae l-XXXXVIII may be useful for the treatment of insulinoma (pancreatic islet cell tumors), e.g. malignant insulinomas and multiple insulinomas, adipose cell carcinomas, e.g. lipocarconoma.
The compounds of the invention are also believed to be useful for the treatment of phaechromocytoma and other diseases with increased catecholamine incretion. The compounds of the invention are also believed to be useful for the treatment of prostate cancer, e.g. adenocarcinoma.
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the
treatment of hepatic steatosis.
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the
treatment of cirrhosis.
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the
treatment of AIDS or an AIDS related diseases, condition or disorders
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the
treatment of lipodystrophy
In still another aspect, the compounds of general formulae l-XXXXVIII may be useful for the
treatment of lactic acidosis.
In yet another aspect, the compounds of the present invention are expected to be useful for
the treatment of CNS diseases, conditions or disorders.

Thus, the compound of the present invention may be used for the treatment of Parkinsons disease, Alzheimers disease, ADHD (Attention Deficit Hyperactivity Disorder), feeding disorders such as bulimia and anorexia, depression, anxiety, cognitive memory disorders, age related cognitive decline, mild cognitive impairment and schizophrenia.
In yet another aspect, the compounds of the present invention may be useful for the treatment of inflammatory disorders, e.g. rheumatoid arthritis, psoriasis, systemic inflammatory response syndrome, sepsis and the like.
The present compounds may also be administered in combination with one or more further pharmacologically active substances eg., selected from antiobesity agents, antidiabetics, antihypertensive agents, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complications and disorders resulting from or associated with obesity.
Thus, in a further aspect of the invention the present compounds may be administered in combination with one or more antiobesity agents or appetite regulating agents. Such agents may be selected from the group consisting of CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melanocortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releasing factor) agonists, CRF BP (corticotropin releasing factor binding protein) antagonists, uro-cortin agonists, p3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, mixed serotonin and noradrenergic compounds, 5HT (serotonin) agonists, bombesin agonists, galanin antagonists, growth hormone, growth hormone releasing compounds, TRH (thyrotropin releasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA agonists (bromocriptin, doprexin), lipase/amylase inhibitors, RXR (retinoid X receptor) modulators or TR (3 agonists.
In one embodiment of the invention the antiobesity agent is leptin. In another embodiment the antiobesity agent is dexamphetamine or amphetamine. In another embodiment the antiobesity agent is fenfluramine or dexfenfluramine. In still another embodiment the antiobesity agent is sibutramine. In a further embodiment the antiobesity agent is oriistat In another embodiment the antiobesity agent is mazindol or phentermine.

Suitable antidiabetics comprise insulin, exendin-4, GLP-1 (glucagon like peptide-1) derivatives such as those disclosed in WO 98/08871 to Novo Nordisk A/S, which is incorporated herein by reference as well as orally active hypoglycaemic agents. The orally active hypoglycaemic agents preferably comprise sulphonylureas, biguanides, meglitinides, glucosidase inhibitors, glucagon antagonists such as those disclosed in WO 99/01423 to Novo Nordisk A/S and Agouron Pharmaceuticals, Inc., GLP-1 agonists, potassium channel openers such as those disclosed in WO 97/26265 and WO 99/03861 to Novo Nordisk A/S which are incorporated herein by reference, DPP-IV (dipeptidyl peptidase-lV) inhibitors, inhibitors of hepatic enzymes involved in stimulation of gluconeogenesis and/or glycogenosis, glucose uptake modulators, compounds modifying the lipid metabolism such as antihyperlipidemic agents and antilipidemic agents as HMG CoA inhibitors (statins), compounds lowering food intake, RXR agonists and agents acting on the ATP-dependent potassium channel of the ceIls.
In one embodiment of the invention the present compounds are administered in combination with insulin.
In a further embodiment the present compounds are administered in combination with a sul-phonylurea eg. tolbutamide, glibenciamide, glipizide or glicazide. In another embodiment the present compounds are administered in combination with a biguanide eg. metformin.
In yet another embodiment the present compounds are administered in combination with a meglitinide eg. repaglinide or senaglinide.
In a further embodiment the present compounds are administered in combination with an a-glucosidase inhibitor eg. miglitol or acarbose.
In another embodiment the present compounds are administered in combination with an agent acting on the ATP-dependent potassium channel of the p-cells eg. tolbutamide, glibenciamide, glipizide, glicazide or repaglinide.
Furthermore, the present compounds may be administered in combination with nategiinide. In still another embodiment the present compounds are administered in combination with an antihyperlipidemic agent or antilipidemic agent eg. cholestyramine, colestipol, clofibrate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucol or dextrothyroxine. In a further embodiment the present compounds are administered in combination with more than one of the above-mentioned compounds eg. in combination with a sulphonylurea and metformin, a sulphonylurea and acarbose, repaglinide and metformin, insulin and a sulphonylurea, insulin and metformin, insulin, insulin and lovastatin, etc.

Furthermore, the present compounds may be administered in combination with one or more antihypertensive agents. Examples of antihypertensive agents are β-blockers such as alpre-nolol, atenolol, timolol, pindolol, propranolol and metoprolol, ACE (angiotensin converting enzyme) inhibitors such as benazepril, captopril, alatriopril, enalapril, fosinopril, iisinopril, quinapril and ramipril, calcium channel blockers such as nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem and verapamil, and a-blockers such as doxazosin, urapidil, prazosin and terazosin. Further reference can be made to Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995. It should be understood that any suitable combination of the compounds according to the invention with one or more of the above-mentioned compounds and optionally one or more further pharmacologically active substances are considered to be within the scope of the present invention.
The present invention also relates to processes according to reaction schemes P, and P2 for the preparation of the above said novel compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts or pharmaceutically acceptable solvates.
Pharmaceutical compositions.
The compounds of the invention may be administered alone or in combination with pharmaceutically acceptable carriers or excipients, in either single or multiple doses. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995. The compositions may appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications.
The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) route, the oral route being preferred. It will be appreciated that the preferred route will depend on the general condition

and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen.
Pharmaceutical compositions for oral administration include solid dosage forms such as capsules, tablets, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings or they can be formulated so as to provide controlled release of the active ingredient such as sustained or prolonged release according to methods well-known in the art.
Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syrups and elixirs.
Pharmaceutical compositions for parenteral administration include sterile aqueous and nonaqueous injectable solutions, dispersions, suspensions or emulsions as well as sterile powders to be reconstituted in sterile injectable solutions or dispersions prior to use. Depot injectable formulations are also contemplated as being within the scope of the present invention.
Other suitable administration forms include suppositories, sprays, ointments, cremes, gels, inhalants, dermal patches, implants etc.
The therapeutic dose of the compound will depend upon the frequency and mode of administration, the sex, age, weight and general condition of the subject treated, the nature and severity of the condition treated and any concomitant diseases to be treated and other factors evident to those skilled in the art. The formulations may conveniently be presented in unit dosage form by methods known to those skilled in the art. In one embodiment the composition in unit dosage form, comprises from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg of the compound of formula I pharmaceutically acceptable salt thereof.
In a still further embodiment the pharmaceutical composition is for oral, nasal, transdermal, pulmonal, or parenteral administration.
For parenteral routes, such as intravenous, intrathecal, intramuscular and similar administration, typically doses are in the order of about half the dose employed for oral administration.

The compounds of this invention are generally utilized as the free substance or as a pharma-ceutically acceptable salt thereof. One example is an add addition salt of a compound having the utility of a free base. When a compound of the invention contains a free base such salts are prepared in a conventional manner by treating a solution or suspension of a free base of the compound with a chemical equivalent of a pharmaceutically acceptable acid, for example, inorganic and organic adds. Representative examples are mentioned above. Physiologically acceptable salts of a compound with a hydroxy group indude the anion of said compound in combination with a suitable cation such as sodium or ammonium ion.
For parenteral administration, solutions of the present compounds in sterile aqueous solution, aqueous propylene glycol or sesame or peanut oil may be employed. Such aqueous solutions should be suitable buffered if necessary and the liquid diluent first rendered isotonic with suffi-dent saline or glucose. The aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous media employed are all readily available by standard techniques known to those skilled in the art
Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solution and various organic solvents. Examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silidc add, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylceliulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may indude any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents.
The pharmaceutical compositions formed by combining the compounds of the invention and the pharmaceutically acceptable carriers are then readily administered in a variety of dosage forms suitable for the disdosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy.

Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules or tablets, each containing a predetermined amount of the active ingredient, and which may include a suitable excipient. These formulations may be in the form of powder or granules, as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion.
If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.
A typical tablet which may be prepared by conventional tabletting techniques may contain:

Core:
Active compound (as free compound or salt thereof) 5 mg
Colloidal silicon dioxide (Aerosil) 1.5 mg
Cellulose, microcryst (Avicel) 70 mg
Modified cellulose gum (Ac-Di-Sol) 7.5 mg
Magnesium stearate q.s.
Coating:
HPMC approx. 9 mg
*Mywacett 9-40 T approx. 0.9 mg
*Acy!ated monoglyceride used as plasticizer for film coating.
The compounds of the invention may be administered to a patient which is a mammal, especially a human in need thereof. Such mammals include also animals, both domestic animals, e.g. household pets, and non-domestic animals such as wildlife.
In a further aspect of the invention the present compounds may be administered in combination with further pharmacologically active substances e.g. an antidiabetic or other pharmacologically active material, including other compounds for the treatment and/or prevention of insulin resistance and diseases, wherein insulin resistance is the pathophysiological mechanism.
Furthermore, the compounds according to the invention may be administered in combination with antiobesity agents or appetite regulating agents.

EXAMPLES.
General Methods
All reactions involving air-sensitive reagents were performed under nitrogen using syringe-septum cap techniques. The glassware were dried by heating with a heath-gun. MgS04 were used to dry solutions. Solvents were removed in vacuo by rotary evaporation. Melting points were recorded on a Buchi 535, Bruker AMX 400 and Bruker DRX 300 instruments were used to record 1H NMR spectra at 400 and 300 MHz respectively with tetramethylsilane (TMS) as internal standard. Coupling constants (J) are given in Hz.
Materials
Test compounds were synthesized or when commercially available they were purchased from Specs, Maybridge, Comgenex, Peakdale or Bionet. For the synthesized compounds the procedure for synthesis and measured characteristics of the compound are stated in the example. All compounds for which no synthesis procedure is stated in the examples are commercially available and have been purchased, or were prepared by standard methods described in the literature.
N-methyl-phenethylcarbamoyl chloride was prepared from N-methyl-phenethylamine and phosgene using triethylamine as a base in dichloromethane. 1-Methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1 -ium iodide, 3-(3,4-dihydro-2H-quinoline-1 -carbonyl)-1 -methyI-3H-imidazol-1-ium iodide and 1-methyl-3-(methyi-phenyl-carbamoyl)-3HnmidazoH-ium iodide was prepared as described by Batey, R.A., Tetrahedron Lett. 39,1998, 6267.
1-Hydroxypyrazole was prepared as described in Begtrup, Vedso, J. Chem. Soc. Perkin Trans 1,1995, 243. 1-hydroxy-4-bromopyrazole was prepared as described in Balle et alM J. Org. Chem. 64,1999, 5366.1-hydroxy-3-(4-methoxyphenyI)pyrazole was prepared as described in Eskildsen et al., J. Org. Chem. 2001 (in press). 1-hydroxyimidazo!e was prepared as described in Eriksen et al., J. Org. Chem, 63,1998,12,1-hydroxy-1,2,3-triazole was prepared as described in Uhlmann et al., J. Org. Chem. 62,1997, 9177.
2-Piperidin-4-ylmethyl-1,2,3,4-tetrahydro-isoquinoline, cyclohexyl-methyl-piperidin-4-ylmethyl-amine, methyl-phenethyl-piperidine-4-ylmethyl-amine, ethyl-piperidin-4-ylmethyl-

piperidin-4-yimethylamine, benzyI-methyl-piperidin-4-ylmethyl-amine, benzyl-ethyl-piperidin-4-ylmethyl-amine, methyl-piperidin-4-ylmethyl-piperidin-3-ylmethyl-amine, 1 -piperidin-4-ylmethyl-piperidin-4-ol, 2-piperidin-4-ylmethyl-2,3-dihydro-1 H-isoindole, cyclopropylmethyl-piperidin-4-ylmethyl-amine was prepared from 4-formylpiperidine -1-carboxylic acid tert-butyl ester prepared as described by Ting, P. C. (Bioorg, Med. Chem. Lett, 11,4,491, 2001) and an appropriate amine by a reductive amination (general procedure 19).
Benzylpiperidine-4-yl-amine, methyl-piperidin-4-yl(2-pyridin-2-yl-ethyl-2-amine,clohexyl-methyl-piperidin-4-yl-amine, lsopropyl-methyI-piperidin-4-yl-amine, methyl-phenethyl-piperidin-4-yl-amine, methyl-piperidin-4-yl-pyridin-S-ylmethyl-amine, was prepared from 4-oxopiperidine-1-carboxylic acid tert -butyl ester by a standard reductive amination procedure as described by Mattson R. J. (J. Org. Chem. 55,2552,1990).
Cyclopropyl-piperidin-4-yI"pyridin-4-yimethyl-amine was prepared from 4-(cyclopropyl-pyridin-4-ylmethyl-amino)-piperidine-1-carboxylic acid ferf-butyl ester by a classical N-deprotection reaction (HCI (g) in diethyl ether or ethanol). 4-(Cyclopropyl-pyridin-4-ylmethyl-amino)-piperidine-1-carboxylic acid ferf-butyl ester was prepared from 4-cyclopropylamino-piperidine-1«carboxylic acid ferf-butyl ester and pyridine-4-yI-acetaldehyde by a classical reductive amination procedure as described by Mattson R. J. 4-CyclopropyIamino-piperidine-1-carboxylic acid ferf-butyl ester was prepared from cyclopropylamine and 4-oxopiperidine-1-carboxyiic acid tert -butyl ester by a standard reductive amination procedure as described by Mattson R. J. Cyclopropyl-(2-fluoro-benzyl)-piperidin-4-yl-amine, cyclopropyl-piperidin-4-yl-pyridin-3-ylmethyl-amine, cyclopropylmethyl-piperidin-4-yl-pyridin-3-ylmethyl-amine and cyclopropylmethyl-piperidin-4-yl-pyridin-4-ylmethyl-amine was prepared by a procedure'similar to the one described for cycIopropyl-piperidin-4-yl-pyridin-4-ylmethyl-amine.
Chloroformates were synthesized from the appropriate phenols and phosgene or a phosgene substitute like e.g. trichloromethyl chloroformate as described in K onakahara, Ozaki, Sato, Gold, Synthesis 1993 (1) 103-106, except that the crude product was separated from the diisopropylethylamine hydrochloride by extraction with diethyl ether rather than with THF.
Non-commercial N-monosubstitued piperazines were prepared by alkylation (alkylation procedure as described in e.g. Masaguer, Ravina, Tetrahedron Lett 1996, 37 (29) 5171-5174) of 1-Boc-piperazine, and subsequent removal of. the Boc group under acidic conditions, e.g.

by heating in a mixture of hydrochloric acid and ethanol. N-Monosubstitued homopiprazines and N-monosubstituted 2,5-diazabicyclo[2.2.1]heptanes were prepared in a similar manner.
Thin layer chromatography was performed on Merck DC-Alufolien, silica gel 60 F254 and components were visualized by UV254. Flash chromatography was performed using silica gel Merck 60 size 0.04-0-063 mm and a Quad 12/25 flash system.
Preparative HPLC (Method A).
The system consists of two Gilson 322 pumps equipped with 30 ml pump heads. A Gilson 215 combined autoinjector and fraction collector performs injection and fraction collection. Detection is performed with a Gilson Diode array detector.
Separation is performed on Waters Xterra columns 19.8 mm 100. mm, flow rate 25 ml/min. The most widely used gradient starts at 10 % acetonitrile in water and ends after 11 min on 100 % acetonitrile, the system is buffered by 0.01% TFA. In special cases the gradient is altered to fit the separation need.
Preparative HPLC (Method B)
HPLC Purification:
The following instrumentation is used:
Gilson 306 Pump
Gilson 806 Manometric module
Gilson 811C Dynamic mixer
Gilson UVA/IS-155
Gilson 202 Fraction collector
The instrument is controlled by Gilson Unipoint software.
The HPLC pump is connected to two eluent reservoirs containing:
A: 0.01% TFA in water
B: 0.01% TFA in acetonitrile
The purification is performed at room temperature by injecting an appropriate volume of the sample (preferably 2 ml) onto the column, which is eluted with a gradient of acetonitrile.
The HPLC conditions and detector settings used are as follows :

Column: Waters Xterra MS C-l 8 X 19 x 100 mm
Gradient 50% - 60% acetonitrile. linearly during 12 min at 20 ml/min
Detection: 210 and 270 nm
Preparative HPLC (method C)
The system consists of two Gilson 322 pumps equipped with 30 ml pump heads. Gilson ma-nometric module 805. A Gilson 215 combined autoinjector and fraction collector performs injection and fraction collection. Detection is performed with a Gilson Diode array detector 170. A sample contain 25-100 mg of material dissolved in 0.5-2.0 ml of solvent (minimum water concentration: 10%).
Separation is performed on Waters Xterra, RP™ 7pm, columns 19 mm x 150. mm, flow rate 15 ml/min (sample added with a flow rate of 5 ml/min for about 1 min). The most widely used gradient starts at 5 % acetonitrile in water and ends after 14. min on 95 % acetonitrile. This concentration is maintained for 6 min. The system is buffered with 0.05% TFA In special cases the gradient is altered to fit the separation need. The pooled fractions are evaporated to dryness in vacuo.
HPLC-MS.
The following instrumentation was used:
- Hewlett Packard series 1100 G1312A Bin Pump
- Hewlett Packard series 1100 Column compartment
- Hewlett Packard series 1100 G13 15A DAD diode array detector
- Hewlett Packard series 1100 MSD
The instrument was controlled by HP Chemstation software.
The HPLC pump was connected to two eluent reservoirs containing:.
A: 0.01% TFA in water
B: 0.01 % TFA in acetonitrile
The analysis was performed at 40 °C by injecting an appropriate volume of the sample (preferably 1 onto the column, which is eluted with a gradient of acetonitrile.

The HPLC conditions, detector settings and mass spectrometer settings which were used are as follows:
Column Waters Xterra MS C-18 X 3 mm id
Gradient 10% -100% acetonitriie linear during 7.5 min at 1.0ml/min
Detection 210 nm (analogue output from DAD)
MS lonisation mode API-ES, Scan 100-1000 amu step 0.1 amu
General procedure 1
The phenol (1.0 mmol) was dissolved in tetrahydrofuran (15 ml) in a glass, screw cap vessel, 1,4-diazabicyclo[2.2.2]octane (DABCO) (2.0 mmol) was added together with the respective carbamoyl chloride (2.0 mmol) at room temperature. The reaction mixture was shaken for 16 hours and poured into ethyl acetate (20 ml) and aqueous citric acid (5%; 20 ml). The organic phase was dried and evaporated to give the crude product.
General procedure 2
The phenol (1.0. mmol) was dissolved in acetonitriie (15 ml) in a glass screw cap vessel. Triethylamine (1.0 mmol) was added together with the respective 1-methyl-3H-imidazoM-ium iodide (1.0 mmol) at room temperature. The reaction mixture was shaken for 16-48 hours at 80 °CI cooled to room temperature and evaporated. The evaporated reaction mixture was dissolved in dichloromethane (20 ml) and extracted with aqueous hydrogen chloride (0.1 M; 20 ml). The aqueous phase was extracted with dichloromethane (3 x 20 ml). The combined organic phases were dried and evaporated to give the crude product.
General procedure 3
The respective phenol (1.0 mmol), 3H-imidazol-1-ium iodide (1.0 mmol) and triethylamine (1.0 mmol) in acetonitriie (3 ml) was heated at 50 °C overnight in a closed vial. The crude product was purified by flash column chromatography (Si02, ethyl acetate/ heptane) yielding the respective carbamate.
General procedure 4
Carbonyldiimidazole (3.6 mmol) was suspended in THF (10ml) and the appropriate secondary, amine (3.0. mmol) was added. The reaction mixture was refluxed for 24 to 72 hours until no traces of amine could be detected. The reaction mixture was cooled to room temperature

and the organic phase evaporated to give the crude product of high purity. The crude product was used without further purification.
General procedure 5
The crude imidazole carboxamide (3.0 mmo!) was dissolved in acetonitrile (10 ml) and methyl iodide (12 mmol.) was added at room temperature. The reaction mixture was stirred for 24 to 48 hours before the organic phase was evaporated to give the crude product, which was used without further purification.
General procedure 6
The respective 1,2,4-(1H)-triazoIes were prepared as described by Blaine (US 3308131).
The 1,2,3-(1H)-triazoles were carbamoylated using the following method:. The respective 1,2,4-(1 H)-triazole (2.0 mmol) was dissolved in dimethylformamide (10 ml) in a glass screw cap vessel, 1,4-diazabicyclo[2.2.2]octane (DABCO) (5.0. mmol) was added together with the respective carbamoyl chloride (5.0 mmol) at room temperature. The reaction mixture was stirred for 16 hours, evaporated to dryness and ethyl acetate (20 ml) and aqueous citric acid (5%; 20 ml) was added. The phases were separated and the aqueous phase extracted with ethyl acetate (20 ml). The combined organic phases were dried and evaporated to give the crude product.
General procedure 7
The aryl chloroformate was prepared from the corresponding phenol, trichloromethyl chloro-formate and ethyldiisopropylamine in dichloromethane according to the procedure described by T. Konakahara, T. Ozaki, K. Sato and B. Gold, Synthesis, 1993 (1) 103 -106, except that the crude reaction mixture was used without removal of ethyldiisopropylamine hydrochloride. To a stirred, freshly prepared solution of the aryl chloroformate in dichloromethane (1 mmol in 3 ml) at -15 °C was added a solution of the substituted piperazine (1 mmol) in dichloromethane (1 mL). The mixture was stirred at 0 °C for 2 -. 6 h. The solvent was removed in vacuo and the solid residue was triturated with diethyl ether (3 x 5 ml), then with a minute amount of water 04 - 2 ml) to remove the ethyldiisopropylamine hydrochloride, filtered and dried to give the hydrochloride of the respective piperazine-1-carboxylic acid aryl ester.

General procedure 8
To a solution of the N-hydroxyazole (1.0 mmol) and ethyldiisopropylamine (1.5 mmol) in CH2CI2 (3 mL) was added the respective carbamoyl chloride (1.5 mmol) at room temperature. The reaction mixture was stirred for 16 hours, added CH2CI2 (20 mL) and washed-with aqueous citric acid (5%; 3x20 mL). The organic phase was separated, dried (MgS04) and evaporated to give the crude product.
General procedure 9
A solution of the substituted piperazine in diethyl ether is added to a stirred solution of an equimolar amount of the aryl chloroformate (prepared from the corresponding phenol by conventional methods) in the same solvent at 0 °C. After completion of the addition, the mixture is stirred at 0 °C for 1 hour, then for 1 more hour at room temperature. The mixture is filtered, the filter cake rinsed with diethyl ether and dried to give the hydrochloride of the respective piperazine-1-carboxylic acid aryl ester.
General procedure 10
A disbstituted amine (1.0 eq) and diisopropylethylamine (1.5 eq) was added to a dried reaction flask under nitrogen. Dichloromethane or tetrahydrofuran was added to give a 0.5 mM concentration of the amine. The appropriate aryl chloroformate (1.0 eq) (prepared from the corresponding phenol by conventional methods) was dissolved in a minimum amount of dichloromethane or tetrahydrofuran and added drop by drop at room temperature. The reaction mixture was stirred overnight, citric acid (5%) was added, and the two phases separated. The aqueous phase was extracted twice with dichloromethane, the combined organic phases were dried with MgS04l filtered and evaporated to give the crude product.
General procedure 11
An appropriate amine (1.0 eq.) was dissolved in dichloromethane (0.5 mM concentration of the amine) in a dried reaction flask under nitrogen. The appropriate aryl chloroformate (1.0 eq.) (prepared from the corresponding phenol by conventional methods) was dissolved in a minimum amount of dichloromethane and added drop by drop at room temperature. Heptane was added to give a 20% solution in dichloromethane and the crude product was isolated by filtration. The crude product was washed with a mixture of dichloromethane/heptane (5:1) and dried in vacuum.
General procedure 12

An appropriate amine (1.0 eq.) and diisopropylethylamine (1.0 eq.) was dissolved in tetrahydrofuran (0.5 mM concentration of the amine) in a dried reaction flask under nitrogen. The appropriate aryi chloroformate (1.0 eq.) (prepared from the. corresponding phenol by conventional methods), was dissolved in a minimum amount of tetrahydrofuran and added drop by drop at room temperature. Acetic acid was added to the reaction mixture (pH 3-5) and the reaction mixture filtered. The organic phase was evaporated and the crude product subjected to preparative HPLC.
General procedure 13
4-(Methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester (1 eq.), diisopropylethylamine (1.5 eq.) was dissolved in tetrahydrofuran (50 mM of phenol).The reaction mixture was added to a mono or disubstituted amine. The reaction mixture was stirred at 50 °C for 16 hours. Citric acid (5%) and terf-butyl-methylether was. added and the. two phases separated. The organic phase was evaporated to give the crude product.
General procedure 14
The phenol (1.0 mmol) was dissolved in tetrahydrofuran (15 ml) in a glass screw cap vessel, 1,4-diazabicyclo[2.2.2]octane (DABCO) (2.0 mmol) was added together with the respective carbamoyl chloride (2.0 mmol) at room temperature. The reaction mixture was shaken for 16 hours. Acetic acid was added to the reaction mixture (pH 3-5) and the reaction mixture filtered. The organic phase was evaporated and the crude product subjected to preparative HPLC.
General procedure 15
A solution of the substituted piperazine in diethyl ether was added to a stirred solution of an equimolar amount of the aryl chloroformate in the same solvent at 0. °C. After completion of the addition, the mixture was stirred at ambient temperature for 1-2 hours. Stirring was discontinued and as much as possible of the solvent was removed by decantation. The residue was rinsed twice with ether by stirring and subsequent decantation and finally dried on a rotary evaporator to give the hydrochloride of the respective piperazine-1-carboxylic acid aryl ester.
If necessary, further purification was achieved by treating the crude product with a mixture of ethyl acetate and a slight excess of sodium bicarbonate (approx. 1.1 eqv.) in water, extracting the. aqueous phase twice with ethyl acetate, drying the combined extracts, filtering and evaporating to give the piperazine-1-carboxylic acid aryi ester as a free base.

General procedure 16
To a solution of the A/-hydroxyazole (1.0 mmol) and ethyldiisopropylamine (1.0 mmol) in CHCl3 (1 mL) at -30 °C was added trichloromethyl chloroformiate (1.1 mmol). The solution was stirred at -30 °C. for. 10 min and at room temperature for 1 h. The solution was evaporated to dryness at room temperature and redissolved in CHCI3 (2 mL) and cooled to -30 °C before addition of the appropriate piperazine (3 mmol). The solution was allowed to warm to room temperature over 30 min and evaporated to give the crude product.
General procedure 17
To a suspension of N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyI)phenyl ester, as its TFA salt (0.5 mmol) and an aryl sulfonyl chloride(0.75 mmol) in CH2CI2 (2 mL) was added DIPEA (1.25 mmol). The reaction mixture was stirred at rt for 2-16 h, and evaporated to dryness and redissolved in MeCN and purified by preparative HPLC (Gilson).
General procedure 18
A solution of the substituted piperazine in diethyl ether was added to a stirred solution of an equimolar amount of the aryl chloroformate in the same solvent at 0 °C. Then an equimolar amount of diisopropylethylamine (DIPEA) in diethyl ether solution was added and the mixture was stirred at ambient temperature for 1 - 2 hours. The solvent was removed on a rotary evaporator and the residue was partitioned between ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate and the combined organic phases were dried and filtered. Removal of the solvent gave the piperazine-1-carboxylic acid aryl ester.
General procedure 19
4-Formyl-piperidine-1-cart)oxylic acid ferf-butyl ester (1.5 g, 7.03 mmol) prepared as described by Ting, P. C. was added to a dryed screw cap wessel under nitrogen. The appropriate amine (7.03 mmol) methanol (10 ml) and acetic acid 100 (\x\) was added and the reaction mixture was stirred for 2 h. at room temperature. Sodium cyanoborohydride (1.0 M sol. In THF, 4.7 ml) was added during 1 minute and the mixture was stirred for 16 h. at room temperature. The reaction mixture was evaporated to dryness and extracted with dichloro-methane (3 x 75 ml) from a 10 % aqueous sodium hydrogene carbonate solution (100 ml). The organic phases were pooled, dryed, and evaporated to dryness to give the crude inter-

mediate, which was subjected to flash chromatography (ethyl acetate/heptane/methanole, 1:2:0-- 4:0:1).
A 3M solution of hydrogen chloride (50 ml) was added to the intermediate and the reaction micture was stirred for 16 h. The reaction mixture was evaporated to dryness to give the crude product, which was dryed in vacoum. The crude product was used without without further purification.
General procedure 20
The arylboronic acid (1.2 mmol), KF (3.3 mmol), Pd2(dba)3 (0.03 mmol) and Pd(P(f-Bu)3)2 (0.06 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Next the aryl halide (1.0 mmol) in THF (2 mL) was added. The reaction mixture was stirred at rt for 16 h.
General procedure 21
To a suspension of methyl-phenyl-carbamic acid 4-amino-phenyl ester (0.5 mmol), (see preparation below) and an aryl sulfonyl chloride (0.75 mmol) in CH2CI2 (2 mL) was added DIPEA (1.25 mmol). The reaction mixture was stirred at rt for 2-16 h, and evaporated to dryness and redissolved in MeCMand purified by preparative HPLC (Gilson).
General procedure 22
A solution of 1-benzyloxy-4-iodobenzene (4.1. mmol) in dry THF (20 mL) was cooled to -78 °C. n-Butyllithium (1.57 M in hexanes, 4.1 mmol) was added during 2 min. After the mixture was stirred for another 5 min, an aryl aldehyde (4.1 mmol) was added. The mixture was allowed to warm to rt during 20 min and quenched with aqueous NaHC03. Extraction with CH2CI2, drying (MgS04), filtration and evaporation provided the crude diarylmethanols which were recrystallised from EtOAc-heptane. A solution of the diarylmethanol product (2 mmol), Nal (14 mmol) in dry MeCN (20 mL) was added trimethylsilyl chloride (14 mmol) and stirred at 80 °C for 19 h. The purple reaction mixture was evaporated to dryness and treated with an aqueous solution of Na2S03. The 4-arylmethylphenols were isolated by filtration or after extraction with CH2CI2 and subsequent purification by flash chromatography (Quad flash 12, EtOAc-heptane).

General procedure 23
A solution of the sulfonamide (0.2 mmol), 37% aqueous formaldehyde (0.5 mL), anf TFA (2 mL) was heated, in a closed vessel in a Smith Creator microwave oven for 300 s at 150 °C. The crude product was evaporated to dryness and purified by preparative HPLC (Gilson).
General procedure 24
A suspention of the phenol (1.0 mmol), 1,4-diazabicyclo[2.2.2]octane (DABCO) (1.5 mmol) and 3-[4-(tert-butyl-dimethyl-silanyloxy)-piperidine-1 -carbonylj-l -methyl-3H-imidazol-1 -ium; iodide (1.5 mmol) in CH2CI2 (1 mL) was stirred at room temperature for 16 hours. The crude product was purified by flash chromatography (Quad flash. 12, EtOAc-heptane). The purified tert-butyldimethylsilyl ether was desilylated by stirring with a 3.2 M solution of HCI in Et20 (20 mL) for 3 h at rt.
General procedure 25
A solution of an alcohol (0.4 mmol), a phenol (0.4 mmol), diisopropylethylamin (0.44 mmol) and tributylphosphine (0.5 mmol) in THF (2 mL) was stirred under nitrogen at rt. ADDP (0.5 mmol) dissolved in THF (2 mL) was added and the reaction mixture was stirred at rt for 16 h, filtered, evaporated to dryness and redissolved in MeCN and purified by preparative HPLC (Gilson).
General procedure 26
A solution of an alcohol (0.4 mmol), a phenol/thiophenoI/N-hydroxyazole/azole or imide (0.4 mmol), diisopropylethylamin (0.44 mmol) and solid supported triphenylphosphine (3 mmol/g, 1.2 mmol) in CH2CI2 (2 mL) was stirred under nitrogen at rt. Di-tert-butylazodicarboxylate (DBAD, 1.2 mmol) dissolved in CH2CI2 (1 mL) was added and the reaction mixture was stirred at rtfor 16 h. TFA (0.5 mL) was added and the mixture was stirred for further 1 h at rt. Addition of EtOAc, filtration, followed by evaporation to dryness gave a crude which was either purified by flash chromatography (Quad flash 12, EtOAc-heptane) or redissolved in MeCN and purified by preparative HPLC (Gilson).

Preparation of 1-methyl-3H-imidazol-1-ium iodides
1 -Methyl-3-(7-trifluoromethyI-3,4-dihydro-2H-quinoIine-1 -carbonyl)-3H-imidazol-1 -ium iodide
Step A:The title product was prepared from 7-(trifluoromethyl-1,2,3,4-tetrahydroquinoline,
as described in the general procedure 4. Light yellow oil. HPLC-MS: m/z = 296.1 (M+1); Rt:
2.85 min.
ΔH(300MHZ; CDCI3): 2.11 (qi, 2H), 2.93 (t, 2H), 3.90 (t, 2H), 7.01 (s, 2H), 7.05 (s, 1H), 7.34
(s, 1H), 7.34 (d, 1H), 7.77 (s, 1H).
Step B: iodide
The title product was prepared from imidazol-1-yI-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-yI)-methanone, as described in the general procedure 5. Light yellow crystals. HPLC-MS: m/z = 310.2 (M+1), Rt: 1.84 min.
ΔH(300MHZ; CDCI3): 2.01 (qi, 2H), 2.94 (t, 2H), 3.83 (t, 2H), 3.92 (s, 3H), 7.52 (s, 2H), 7.76 (s, 1H), 7.80 (s, 1H), 7.85 (s, 1H), 9.62 (s, 1H).
3-(cyclohexyl-methyl-carbamoyl)-1 -methyl-3H-imidazol-1 -ium iodide
Step A: lmidazole-1-carboxylic acid cyclohexyl-methyl-amide
The title product was prepared from cyclohexyl-methyl-amine, as described in the general procedure 4. Off-white crystals. HPLC-MS: m/z = 208.1 (M+1)f Rt: 1.85 min δH(300MHz; CDCI3): 1.05-1.22 (m, 1H), 1.25-1.45 m, 2H), 1.50-1.61 (dt, 2H), 1.63-1,75 (d, 1H), 1.76.1.95 (m, 4H), 3.80-3.95 (m, 1H), 7.09 (bs, 1H)f 7.21 (bs 1H), 7.87 (bs, 1H).
Step B: 3-(cyclohexyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide

The title product was prepared from imidazoIe-1-carboxyiic acid cyclohexyl-methyl-amide, as
described in the general procedure 5. Yellow crystals; HPLOMS: m/z = 222.2 (M+1), Rt:
1.15 min.
δH(300MHz; CDCI3): 1.03-1.25, (m, 1H), 1.30-1.60 (m, 4H), 1.62-11.78 (m, 1H), 1.82-2.00 (t,
4H), 3.21 (s, 3H), 3.90-4.10 (m, 1H), 4.29 (s, 3H), 7.52 (bs, 1H), 7.66 (bs, 1H), 10.37 (bs,
1H).
3-(2,6-dimethyl-morpholine-4-carbonyl)-1 -methyI-3H-imidazoI-1 -ium iodide
Step A: {2.6-Dimethvl-morpholinδHvl)-imidazol-1-vl-methanone
The title product was prepared from 2,6-dimethyI-morphoIine, as described in the general procedure 4. Colourless oil. PPLOMS: m/z = 210.10 (M+1), Rt: 0.63 min. ΔH(300MHZ; CDCI3): 1.20 (s, 3H), 1.22 (s, 3H)f 2.82 (dd, 2H), 3.60-3.75 (m, 2H), 3.93 (d, 2H), 7.11 (s, 1H), 7.20 (s, 1H), 7.87 (sf 1H).
Step B:The title product was prepared from, (2,6-Dimethyl-morpholin-4-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Light yellow oil; HPLOMS: m/z = 224.2 (M+1), Rt: 0.40 min.
ΔH(300MHZ; CDCI3): 1.23 (s, 3H), 1.25 (s, 3H), 2.90-3.10 (m, 2H), 3.7-3.9 (m, 2H), 3.95-4.15 (m, 2H), 4.26 (s, 3H), 7.67 (s, 1H), 7.73 (s, 1H)10.05 (s, 1H).
3-(Benzyl-methyl-carbamoyI)-1 -methyl-3H-imidazol-1 -ium iodide Step A: lmidazole-1-carboxylic acid benzyl-methyl-amide
The title product was prepared from benzyl-methyl-amine, as described in the general procedure 4. Light yellow crystals. HPLC-MS: m/z = 216.1 (M+1), Rt: 1.53 min. (300MHz; CDCI3): 3.04 (s, 3H), 4.65 (s, 3H), 7.08 (bs, 1H), 7.22-7.34 (m, 3H), 7.34-7.50 (m, 3H),7.93(bs, bs, 1H).

Step B: 3-(Benzyl-methyl-;arbamoyQ-1-methyl-3H-imidazol-1-ium iodide
The title product was prepared from imidazole-1-carboxylic acid benzyl-methyl-amide, as described in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 230.1 (M+1), Rt: 1.23 min.
ΔH(300MHZ; CDCI3): 3.25 (s, 3H), 4.2 (s, 3H), 4.76 (s, 2H), 7.27-7.50 (m, 5H), 7.56 (bs, 1H), 7.70(bs, 1H), 10.29 (bs,1H).
3-(Phenyl-ethyl-carbamoyl)-1 -methyl-3H-imidazol-1 -ium iodide
Step A: lmidazole-1~carboxylic acid phenyl-ethyl-amide
The title product was prepared from phenyl-ethyl-amine, as described in the general procedure 4. Light brown oil. HPLC-MS m/z = 216.1 (M+1), Rt: 1.75 min. δH(300MHz; CDCI3): 1.26 (t, 3H), 3.92 (q, 2H), 6.79 (s, 1H), 6.84 (s, 1H), 7.10 (d, 2H), 7.27-7.45 (m,3H), 7.55 (s,1H);
Step B: 3-(Phenyl-ethyl-carbamoyI)-1-methyl-3H-imidazol-1-ium iodide
The title product was prepared from imidazole-1-carboxylic acid phenyl-ethyl-amide, as described in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 230.2 (M+1), Rt: 1.16 min.
δH(300MHz; CDCI3): 1.28 (t, 3H), 3.96 (q, 2H). 4.10 (s, 3H), 7.03 (s, 1H), 7.27 (s, 1H), 7.35-7.60 (m, 6 H), 9.70 (s, 1H).
3-(2,3-Dihydro-indole-1 -carbonyl)-1 -methyI-3H-imidazoM-ium iodide
Step A: (2.3~Dihvdro-indol-1-vI)-imidazol-1-vl-methanone
The title product was prepared from Indoline, as described in the general procedure 4. Pink crystals. HPLC-MS m/z = 214.1 (M+1), Rt: 1.62 min.

ΔH(300MHZ; CDCI3): 3.21 (t, 2H), 4.21 (t, 2H), 7.21 (dt, 1H, 7.15 (s, 1H), 7.17-7.29 (m, 2H)f 7.36 (t, 1H), 7.40 (d, 1H), 8.03 (bs, 1H).
Step B:
The title product was prepared from (2f3-dlhydro-indol-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Light brown crystals. HPLC-MS m/z = 228.1 (M+1), Rt: 0.94 min.
δH(300MHz; CDCI3): 3,42 (t, 2H), 4.34 (s, 3H), 4.71 (t( 2H), 7.17-7.36 (m, 4H), 7.78 (bs, 1H), 7.86 (d, 1H), 10.76 (bs, 1H).
3[(4-ChIorophenyl)-methyl-carbamoyI]-1 -methyl-3H-imidazol-1 -ium iodide Step A: lmidazole-1-carboxylic acid (4-chloro-phenyl)-methyl-amide
The title product was prepared from 4-chlor-N-methylaniline, as described in the general procedure 4. Light yellow crystals. HPLC-MS m/z = 236.1 g/mol (M+1), Rt: 1.91 min. ΔH(300MHZ; CDCI3): 3.47 (s, 3H)( 6.85 (s, 1H), 6.87 (s, 1H), 7.06 (d, 2H), 7.36 (d, 2H), 7.60 (s, 1H).
Step B: [(4-Chlorophenyl)-methytearbamoyI]-1wethyl-3H-imδH iodide
The title product was prepared from imidazole-1-carboxylic acid (4-chloro-phenyl)-methyI-amide, as described in the general procedure 5. Orange crystals. HPLC-MS m/z = 250.1 (M+1), Rt: 1.06 min.
sh(300MHz; CDCI3): 3.55 (s, 3H), 4.12 (s, 3H), 7.16 (bs, 1H), 7.35 (t, 1H), 7.41 (d, 1H), 7.45 (t, 1H), 7.51 (t, 1H), 7.53-7.55 (m, 1H), 9.92 (bs, 1H).
3-{isopropyl-methyI-carbamoyI)-1 -methyi-3H-imidazol-1 -ium iodide
Step A: lmidazole-1-carboxylic acid isopropyl-methyl-amide

The title product was prepared from isopropyl-rnethylamine, as described in the general procedure 4. Light yellow oil. HPLC-MS m/z = 168.1 (M+1), Rt 0.51 min. ΔH(300MHZ; CDCI3): 1.25 (s, 3H), 1.27 (s, 3H), 2.93 (s, 3H), 4.36 (Qi, 1H), 7.08 (bs( 1H), 7.22 (bs, 1H),7.88(bs, 1H).
Step B: 3δHisopmpyl-methylδHarbamoyl)-1-methyl-3H-imidazol~1-ium iodide
The title product was prepared from imidazole-1-carboxylic acid isopropyl-methyl-amide, as described in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 182.2 (M+1), Rt: 0.41 min.
δH(300MHz; CDCI3): 1.31 (s, 3H), 1.35 (s, 3H), 3.17 (s, 3H), 4.29 (s, 3H)f 4.30-4.50 (m, 2H), 7.62 bs, 1H), 7.71 (bs, 1H), 10.29 (bs, 1H).
3-(1,3-Dihydroisoindole-2-carbonyl)-1 -methyl-3H-imidazoM -ium iodide
Step A: (1,3-Dihydroisoindole-1-yl)-imidazol-1-yI-methanone
The title product was prepared from isoindole, as described in the general procedure 4. Oil. Step B: 3-(1,3-Dihydmisoindole-2δHarbonyl)-1-methyl-3H-imidazol-1-ium iodide
The title product was prepared from (1,3-dihydroisoindole-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Crystals.
ΔH(300MHZ; CDCI3): 3.96 (s, 3H), 4.98 (s, 2H), 5.04 (s, 2H), 7.35 (bs, 3H), 7.44 (bs, 1H), 7.91 (s, 1H), 8.21 (s,1H), 9.74 (s,1H).
1 -MethyI-3-(piperidine-1 -carbonyl)-3H-imidazoI-1 -ium iodide Step A: Pioeridin-1-vHmidazol-1-vl-methanone
The title product was prepared from piperidine, as described in the general procedure 4. Oil. Step B: 1-Methyl-3-(piperidine-1-carbonyO-3H-imidazol~1-ium iodide

The title product was prepared from piperidin-l-yl-imidazoH-yl-methanone, as described in the general procedure 5. Oil.
c(300MHz; CDCi3): 1.74 (s, 6H), 3.66 (bs, 4H), 4.28 (s, 3H)f 7.78 (s, 1H)( 7.83 (s, 1H), 10.07 (s,1H).
1 -Methyl-3-(2-methyl-piperidine-1 -carbonyl)-3H-imidazoI-1 -ium iodide Step A: (2-Methyl-piperidin-1-yl)-imidazQl-1-yl-methanone
The title product was prepared from 2-methyl-piperidine, as described in the general procedure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rfc 0.92 min. δH(300MHz; CDCI3): 1.33 (d, 3H) 1.45-1.67 (m, 2H)f 1.68-1.85 (m, 4H), 3.17 (dt, 1H), 3.86 (dd, 1H), 4.35-4.50 (m, 1H), 7.09 (s, 1H), 7.18 (s, 1H), 7.84 (s, 1H).
Step 5:1-MethyI-3-(2-methyl-piperidine-1-carbonyl)-3H-imidazo iodide
The title product was prepared from (2-methyI-piperidin-1-yl)-imidazol-1-yl-methanone, as
described in the general procedure 5. Orange solid. HPLC-MS m/z = 208.1 (M+1), Rt:
0.57min.
δH(300MHz; CDCI3): 1.40 (d, H),1.60-1.98 m, 6H), 3.45 (t, 1H), 3.90 (d, 1H), 4.30 (s, 3H),
4.45-4.60 (m, 1H)( 7.59 (s, 1H), 7.62 (s, 1H), 10.06 (s, 1H).
1 -Methyl-3-{3-methyl-piper!dine-1 -carbonyl)-3H-imidazol-1 -ium iodide
Step A: (3-Methvl-Diperidin-1-v!)-imidazol-1-vI-methanone
The title product was prepared from 3-methyl-piperidine, as described in the general procedure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rt: 1.15 min.
c(300MHz; CDCI3): 0.94 (d, 3H), 1.05-1.35 (m, 1H), 1.50-2,00 (m, 4H), 2.67 (t, 1H), 3.01 (dt, 1H), 3.98 (t, 2H), 7.09 (s, 1H), 7.19 (s, 1H), 7.85 (s, 1H).
Step B:

The title product was prepared from (3-methyl-piperidin-1-yI)-imida2oH-yI-methanone, as described in the general procedure. 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt 0.69min. ΔH(300MHZ; CDCI3): 0.97 (d, 3H), 1,15-1.40 (m, 1H), 1.55-2.00 (m, 4H), 2.92 (t, 1H), 3.28 (t, 1H), 3.90-4.15 (m, 2H), 4.28 (s, 3H), 7.60-7.75 (m, 2H), 10.14 (s, 1H).
1 -Methyl-3-(4-methyl-piperidine-1 -carbonyl)-3HHrnidazol-1 -ium iodide Step A: (4-Methvl-piperidin-1-vl)~imidazol-1-vl-methanone
The title product was prepared from 4-methyl-piperidine, as described in the general procedure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rt 1.32 min. δH(300MHz; CDCI3): 100 (d, 3H), 1.15-1.35 (m, 2H), 1.55-1.85 (m, 3H), 3.02 (dt, 2H), 4.08 (d, 2H), 7.08 (s, 1H), 7.19 (s, 1H), 7.85 (s, 1H).
Step B: 1-Methyl-3-(4-methyl-piperidine-1 The title product was prepared from (4-methyl-piperidin-1-yI)-imidazol-1-yl-methanoneI as described in the general procedure 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt 0.65min. (300MHz; CDCI3): 1.00 (d, 3H), 1.20-1.50 (mt 2H), 166-190 (m, 3H), 3.32 (t, 2H), 4.13 (d, 2H), 4.28 (s, 3H), 7.58 (s, 1H), 7.64 (s, 1H)f 10.15 (s, 1H).
1 -Methyl-3-(4-benzyl-piperidine-1 -carbonyI)-3H-imidazol-1 -ium iodide Step A: (4-Benzvl-piDeridin-1-vI)-imidazol-1-vl-methanone
The title product was prepared from 4-methyl-piperidine, as described in the general procedure 4. light yellow oil. HPLC-MS m/z = 270.2 (M+1), Rt 2.58 min. sh(300MHz; CDCI3): 110-150 (m, 2H), 165-2.00 (m, 3H), 2.59 (d, 2H), 2.97 (dt, 2H), 4.08 (d, 2H), 7.05-7.40 (m, 7H), 7.84 (s, 1H).
Step B: 1-Methyl-3δH(4-benzyl-pipendine-1-carbonyl)-3H-imidazoM'ium iodide
The title product was prepared from (4-benzyl-piperidin-1-yl)-im'dazol-1-yl-methanone, as described in the general procedure 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt 0.65min.

δH(300MHz; CDCI3): 1.30-1.50 (m, 2H), 1.75-1.95 (m, 3H), 2.59 (df 2H), 3.15-3.40 (m, 2H), 4.05-4.20 (m, 2H), 4.25 (s, 3H), 7.10-7.35 (m, 5H), 7.45 (bs, 1H), 7.60 (bs, 1H), 10.22 (s, 1H).
1 -Methyl-3-(1,2,3,4-tetrahydroisoquinoline-1 -carbony!)-3H-imidazoI-1 -ium iodide Step A: (1.2.3,4-Tetrahvdroisoauinolme'1-vI)-imidazol-1-vl-methanone
The title product was prepared from 1,2,3,4-tetrahydroisoquinoIine, as described in the general procedure 4. Oil.
Step B: 1-Methyl-3-(1,2,3,44etrahydroisoquinoline-1-carbony
The title product was prepared from (1,2,3,4-tetrahydroisoquinoIine-l-yIHmidazoM-yl-methanone, as described in the general procedure 5. Oil.
(ΔH(300MHZ; CDCI3): 2.97 (t, 2H), 3.73 (bs, 2H), 3.94 (s, 3H), 4.75 (s, 2H), 7.15-7.35 (m, 4H), 7.88 (d, 1H), 8.09 (d, 1H), 9.63 (s, 1H).
Preparation of Phenols
1-(4-Hydroxy-phenyl)-4,4-dimethyl-piperidine-2,6-dione
A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3,3-dimethyigIutaric anhydride (4.26 g, 30.0 mmol) was heated in a round bottom flask at 165 °C for 1 h, followed by heating at 180 °C for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was evaporated and the residue was crystallised from water/ethanol yielding the title compound (3.51 g, 50% yield, pink solid). 1H NMR (300 MHz, DMSO-d6): £1.08 (s, 6H), 2.63 (s, 4H), 6.77 + 6.86 (AB-system, 4H), 9.56 (s,1H).

c/s-2-{4-Hydroxy-phenyI)-hexahydro-isoindoIe-1,3-dione
A mixture of 4-aminophenoI (5.46 g, 50.0 mmol) and c/s-1,2-cydohexanedicart-oxylic anhydride (7.71 g, 50.0 mmol) was heated in a round bottom flask at 170 °C for 2 h. After cooling to room temperature the solid material was dissolved in hot ethanol (200 ml), activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was partially evaporated. The solids were collected by filtration, washed quickly with a small amount of ethanol and dried in vacuo at 40 °C yielding the title compound (8.52 g, 69% yield, pink solid).
1H NMR (300 MHz, DMSO-cfe): £1.38 (m, 4H), 1.73 (m, 4H), 3.02 (m, 2H), 6.82 (d, 2H), 7.02 (d, 2H), 9.66 (s, 1H, OH); HPLC-MS: m/z = 246 (M+1); Rt = 2.53 min.
Cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide
To a solution of 4-aminophenol (5.00 g, 45.8 mmol) in dichloromethane (50 ml) were added cyclohexanecarbonyl chloride (6.72 g, 45.8 mmol) and pyridine (3.70 ml, 45.8 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. Water (100 ml) was added, the organic phase was removed and the resulting solution was extracted with ethyl acetate (3 x 300 ml).. The combined organic phases were washed with water (2 x 200 ml), dried, filtered and evaporated, yielding an off-white solid. The crude product was purified by flash column chromatography (Si02, ethyl acetate/heptane (40:60)), yielding a mixture of two compounds, which were dissolved in THF. 6N NaOH (aq, 32 ml) was added and the mixture was stirred at room temperature for 2.5 h. The solution was acidified with concentrated hydrochloric acid and the organic solvent was removed by evaporation. The solid material was collected by filtration, dried and recrystallised from ethyl acetate/heptane, yielding the title compound (4.20 g, 41%, off-white solid).
1H NMR (300 MHz, DMSO-of6): £1.12-1.48 (m, 5H), 1.65 (m, 1H), 1.70-1.82 (m, 4H), 2.27 (m, 1H), 6.66 (d, 2H), 7.36(d, 2H), 9.10 (s, 1H), 9.50 (s, 1H); HPLC-MS: /n/z= 220 (M+1); Rt = 2.69 min.

2-Cyclohexyl-N-(4-hydroxy-phenyl)-acetamide
To a solution of 4-aminophenol (3.83 g, 35.1 mmo!) in dichioromethane (50 ml) were added cyclohexylacetyl chloride (11.26 g, 70.1 mmol) and pyridine (5.67 ml, 70.1 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 41 ml) was. added and the mixture was stirred at room temperature for 4 h. The solution was acidified with 1 N hydrochloric acid. The solvent was removed by evaporation. The solid material was collected by filtration, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (5.5 g) in methanol (50 ml) was added. After stirring for 1 h at room temperature water (200 ml) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI. The solid material was isolated by filtration and dried in vacuo at 40 °C yielding the title compound (6.31 g, 77% yield, pink crystals).
1H NMR (200 MHz, DMSO-of6): £0.82-1.32 (m, 5H), 1.54-1.76 (m, 6H), 2.12 (d, 2H), 6.66 (d, 2H), 7.32 (d, 2H), 9.12 (s, 1H). 9.57 (s, 1H); HPLC-MS: m/z = 234 (M+1); Rt= 3.09 min.
c/s/trans-4-tert-Butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide
To a solution of 4-aminophenol (3.08 g, 28.2 mmol) in dichioromethane (50 ml) were added c/s/frans-4-tert-butyl-cyclohexanecarbonyl chloride (11.43 gf 56.4 mmol) and pyridine (4.56 ml, 56.4, mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 33 ml) was added and the mixture was stirred at room temperature overnight. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material was collected by filtration, washed with water, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (2.4 g) in methanol (50 ml) was added. After stirring for 2 h at room temperature water (200 ml) was added and the organic phase was removed by evaporation. The aqueous phase was acidified with 1 N HCI and extracted with

ethyl acetate (3 x 300 ml). The combined organic phases were washed with saturated sodium bicarbonate, dried, filtered and evaporated, yielding a pink oil, which was dried in vacuo at 40 °C. The solid material was crystallised from ethyl acetate/heptane yielding the. title compound (2.03 g, 26%, pink crystals). From the first aqueous extract a second portion of product was isolated by extraction with ethyl acetate (3 x 250 ml). The combined organic phases were washed with water (400 mf), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated, yielding a pink thick oil. Crystallisation from ethyl acetate/heptane yielded a further amount of title compound (2.75 g, 35%).
1H NMR (300 MHz, DMSO-d6): £0.80 + 0.84 (2 x s, 9H), 0.98 (m, 2H), 1.23-1.57 (m, 4H), 1.76-1.90 (m, 2H), 2.02-2.14 (m, 1.5H), 2.57 (m, 0.5H), 6.65 (d, 2H), 7.34 (d xd, 2H),9.09 (s, 1H), 9.36 + 9.50 (2 x s, 1H); HPLC-MS: mtz = 276 (M+1); Rt = 4.19 and 4.27 min.
N-(4-Hydroxy-phenyl)-3,3-dimethyl-butyramide
To a solution of 4-aminophenol (3.27 g, 30.0 mmol) in dichloromethane (50 ml) were added 3,3-dimethyl-butyryl chloride (8.08 g, 60.0 mmol) and pyridine (4.85 ml, 60.0 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 35 ml) was added and the mixture was stirred at room temperature overnight. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material was collected by filtration, washed with water, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (3.37 g) in methanol (50 ml) was added. After stirring for 2 days at room temperature water (300 ml) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI. The solids were collected by filtration and dried under vacuum at 40 °C yielding the title compound (1.97 g, 31%, pink solid). The mother liquor was extracted with ethyl acetate (3 x 250 ml). The combined organic phases were washed with saturated sodium bicarbonate (2 x 250 ml), dried in vacuo, filtered and evaporated yielding a second amount of the title compound (0.67 g, 10%). From the first aqueous extract another portion of product was isolated by extraction with ethyl acetate (4 x 250 ml). The combined organic phases were washed with water (400 ml), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated yielding a pink thick oil. Crys-

tallisation from ethyl acetate/heptane yielded a third amount of the title compound (2.11 g,
34%).
1H NMR (300 MHz, DMSO-of6): £1.00 (s, 9H), 2.12 (s, 2H), 6.67 (d, 2H), 7.33 (d, 2H), 9.12
(s, 1H), 9.50 (s, 1H); HPLC-MS: m/z= 208 (M+1); Rt = 2.50 min.
1-(4-Hydroxy-phenyl)-4,4-dimethyl-piperidine-2,6-dione
A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3t3-dimethylglutaric anhydride (4.26 g, 30.0 mmol) was heated in a round bottom flask at 165 °C for 1 h, followed by heating at 180 °C for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, ' activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was evaporated and the residue was crystallised (water/ethanol) yielding the title compound (3.51 g, 50%, pink solid). 1H NMR (300 MHz, DMSO-d6): £1.08 (s, 6H), 2.63 (s, 4H), 6.77 + 6.86 (AB-system, 4H), 9.56 (s,1H).
c/s-2-(4-Hydroxy-phenyl)-hexahydro-isoindole-1,3-dione
A mixture of 4-aminophenol (5.46 g, 50.0 mmol) and c/s-1,2-cydohexanedicarboxylic anhydride. (7.71 g, 50.0 mmol) was heated in a round bottom flask at 170 °C for 2 h. After cooling to room temperature the solid material was dissolved in hot ethanol (200 ml), activated charcoal was added and the solution was heated at reflux for 1 h. The solid material was removed by hot filtration. The solvent was partially evaporated. The solids were collected by filtration, washed quickly with a small amount of ethanol and dried in vacuo yielding the title compound (8.52 g, 69%, pink solid).
1H NMR (300 MHz, DMSO-cf6): 51.38 (m, 4H), 1.73 (m, 4H), 3.02 (m, 2H), 6.82 (d, 2H), 7.02 (d, 2H), 9.66 (s, 1H, OH); HPLC-MS: m/z= 246 (M+1); Rt = 2.53 min.

Cyclohexanecarboxylic acid (4-hydroxy-pheny!)-amide
To a solution of 4-aminophenol (5.00 g, 45.8 mmol) in dichloromethane (50 ml) were added cyclohexanecarbonyl chloride (6.72 g, 45.8 mmol) and pyridine (3.70 ml, 45.8 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. Water (100 ml) was added, the dichloromethane was removed by evaporation and the resulting solution was extracted with ethyl acetate (3 x 300 ml). The combined organic phases were washed with water (2 x 200 ml), dried, filtered and evaporated, yielding an off-white solid. The crude product was purified by flash column chromatography (Si02, ethyl acetate/heptane (2:3)), yielding a mixture of two compounds, which were dissolved in THF. 6N NaOH (aq, 32 ml) was added and the mixture was stirred at room temperature for 2.5 h. The solution was acidified with concentrated hydrochloric acid. The THF was removed by evaporation. The solid material was collected by filtration, dried in vacuo and recrystaliised (ethyl acetate/heptane), yielding the title compound (4.20 g, 41%, off-white solid).
1H NMR (300 MHz, DMSO-cf6): (51.12-1.48 (m, 5H), 1.65 (m, 1H), 1.70-1.82 (m, 4H), 2.27 (m, 1H), 6.66 (d, 2H), 7.36 (d, 2H), 9.10 (s, 1H), 9.50 (s, 1H); HPLC-MS: mtz= 220 (M+1); Rt = 2.69 min.
2-Cyclohexyl-N-(4-hydroxy-phenyl)-acetamide
To a solution of 4-aminophenoI (3.83 g, 35.1 mmol) in dichloromethane (50 ml) were added cydohexylacetyl chloride (11.26 g, 70.1 mmol) and pyridine (5.67 ml, 70.1 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 41 ml) was added and the mixture was stirred at room temperature for 4 h. The solution was acidified with 1 N hydrochloric acid and the organic phase was removed by evaporation. The solid material was collected by filtration, dried and dissolved in methanol (100 ml). A solution of KOH (5.5 g) in methanol (50 ml) was added. After stirring for 1 h at room temperature water (200 ml) was added and the organic solvent was removed by evaporation. The aqueous

phase was acidified with 1 N HCI. The title product was isolated by filtration and dried in vacuo. (6.31 g, 77%, pink crystals).
1H NMR (200 MHz, DMSO-d6): 50.82-1.32 (m, 5H), 1.54-1.76 (m, 6H), 2.12 (d; 2H), 6.66 (d, 2H), 7.32 (d, 2H), 9.12 (s, 1H), 9.57 (s, 1H); HPLC-MS: mlz = 234 (M+1); Rt = 3.09 min.
c/s/trans-4-tert-Butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyI)-amide
To a solution of 4-aminophenol (3.08 g, 28.2 mmol) in dichloromethane (50 ml) were added c/s/Trans-4-tert-butyl-cyclohexanecarbonyl chloride (11.43 g, 56.4 mmol) and pyridine (4.56 ml, 56.4 mmol), while cooling the reaction mixture in an ice bath-After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 33 ml) was added and the mixture was stirred at room temperature overnight. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material collected by filtration, washed with water, dried and dissolved in methanol (100 ml). A solution of KOH (2.4 g) in methanol (50 ml) was added. After stirring for 2 h at room temperature water (200 ml) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI and extracted with ethyl acetate (3 x 300 ml). The combined organic phases were dried and evaporated, yielding a pink oil, which was dried in vacuo. The solid material was crystallised from ethyl acetate/heptane yielding the title compound (2.03 g, 26%) as pink crystals. From the first aqueous extract a second portion of product was isolated by extraction with ethyl acetate (3 x 250 ml). The combined organic layers were washed with water (400 ml), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated, yielding a pink thick oil. Crystallisation from ethyl acetate/heptane yielded a second amount of the title compound (2.75 g, 35%). 1H NMR (300 MHz, DMSO-d6): 50.80 + 0.84 (2 x s, 9H), 0.98. (m, 2H), 1.23-1.57 (m, 4H), 1.76-1.90 (m, 2H), 2.02-2.14 (m, 1.5H), 2.57 (m, 0.5H), 6.65 (d, 2H), 7.34 (d x d, 2H), 9.09 (s, 1H), 9.36 + 9.50 (2 x s, 1H); HPLC-MS: mlz = 276 (M+1); Rt = 4.19 and 4.27 min.
N-(4-Hydroxy-phenyI)-3,3-dimethyl-butyramide

To a solution of 4-aminophenol (3.27 g, 30.0 mmol) in dichloromethane (50 ml) were added 3,3-dimethyl-butyryl chloride (8.08 g, 60.0 mmol) and pyridine (4.85 ml, 60.0 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 35 ml) was added, the mixture was stirred at room temperature overnight and the solvent was removed by evaporation. Water (200 ml) was added and the solid material is collected by filtration, washed with water, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (3.37 g) in methanol (50 ml) was added. After stirring for 2 days at room temperature water (300 ml) was added, the organic solvent was removed and the aqueous phase was acidified with 1 N HCI. The solids were collected and dried yielding the title compound (1.97 g, 31 % yield, pink solid). The mother liquor was extracted with ethyl acetate (3 x 250 ml). The combined organic phases were washed with saturated sodium bicarbonate (2 x 250 ml), dried over sodium sulphate, filtered and evaporated yielding a second amount of the title compound (0.67 g, 10%). From the first aqueous extract another portion of product was isolated by extraction with ethyl acetate (4 x 250 ml). The combined organic phases were washed with water (400 ml), dried, filtered and evaporated yielding a pink thick oil. Crystallisation from ethyl acetate/heptane yielded a third amount of the title compound (2.11 g, 34%). 1H NMR (300 MHz, DMSO-cf6): S1.00 (s, 9H), 2.12 (s, 2H), 6.67 (d, 2H), 7.33 (d, 2H), 9.12 (s, 1H), 9.50 (s, 1H); HPLC-MS: mlz= 208 (M+1); Rt = 2.50 min.
4-(3-Trifluoromethyl-phenoxy)-phenol
Hydroquinone monobenzylether (1 g, 5.0 mmol), 3-(trifluoromethyl)-phenyl boronic acid (1.9 g, 10.0 mmol), copper (II) acetate (0.91 g, 5.0 mmol) and triethylamine (2.53 g, 25.0 mmol) were dissolved/suspended in dichloromethane (50 ml). The reaction mixture was stirred for 70 h. at room temperature and evaporated to dryness. The crude intermediate was subjected to flash chromatography (ethyl acetate/heptane (1:4)) (42%) and hydrogenated (10% Pd/C) using ethanol as a solvent. The organic phase was evaporated and aqueous sodium hydroxide (1N, 30 ml) was added together with dichloromethane. The two phases were separated and the aqueous phase extracted with dichloromethane (30 ml x 2). The aqueous phase was acidified with aqueous hydrochloric acid (2N) and extracted with dichloromethane (30 ml x 5). The organic phase was dried and evaporated to give the crude product (47%). HPLC-MS m/z = 254.9 (M+1), Rt: 4.39 min.

ΔH(300MHZ; CDCI3): 6,85 (dt, 2H), 6.94 (dt, 2H), 7.10 (dd, 1H), 7.16 (bs, 1H), 7.24-7.30 (m, 1H),7.39(t,1H).
4-Hydroxy-benzoic acid 2,5-dioxo-pyrroIidin-l-yl ester
4-Hydroxybenzoic acid (30 g, 0.217 mmol) and 4-hydroxysuccinamide (25.32 g, 0,220mmol) were dissolved in 1.4-dioxane (550 ml) at room temperature. After 20 min. the clear solution was cooled to 15°C and dicyclohexylcarbodiimide (44.82 ml, 0.217 mmol) was added. The reaction mixture was stirred for 18 hours and filtered. The organic phase was evaporated to dryness (86 g). Ethanol (250 ml) was added to the crude product and the mixture heated to reflux. The crude product was crystallized from ethanol/water (5:1) (22 g, 43%), and the mother liquor recrystallized from ethanol/water (25 g, 49%). HPLC-MS: mfz = (M+1); Rt: min.
N-(6-Methoxy-pyridin-3-yl)-benzamide
A solution of 5-amino-2-methoxypyridine (2.48 g, 20.0 mmol) and N-ethyldiisopropylamine (2.84 g( 22,0 mmol) in dichloromethane (20 ml) was cooled in an ice-bath. Benzoyl chloride (3.09 g, 22 mmol) was slowly added by means of a syringe. The cooling bath was removed and stirring was continued at room temperature for 18 hours. Dichloromethane was added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo leaving a dark solid. Crystallisation from ethyl ace-tate:heptane yielded the title compound (3.44 g, 75% yield).
1H NMR (300MHz, CDCI3): £3.93 (s, 3H), 6.77 (d, 1H), 7.44-7.59 (m, 3H), 7.81 (br.s, 1H), 7.87 (df 2H), 8.01 (dd, 1H), 8.16 (d, 1H); HPLC-MS (Method A): m/z= 229 (M+H); Rt= 2.52 min.
Cyclohexanecarboxylic acid (6-methoxy-pyridin-3-yl)-amide hydrochloride
5-Amino-2-methoxypyride (3.72 g, 30.0 mmol), dissolved in a small amount of tetrahydrofu-ran, was added slowly to a solution of cyciohexanecarbonyl chloride (4.40 g, 30.0 mmol) in tetrahydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 ml) was added and the solids were collected by suction yielding the title compound (8.12 g, 100% yield) as a purple solid.

1H NMR (300MHz, CDCI3): £1.11-1.48 (m, 5H), 1.63 (m, 1H), 1.68-1.83 (m, 4H), 2.32 (m, 1H), 3.81 (s, 3H), 6.80 (d, 1H), 7.92 (dd, 1H), 8.00 (br.s, 1H), 8.38 (d, 1H), 9.92 (s, 1H); HPLC-MS (Method A): mlz = 235 (M+H); Rt = 2.89 min.
6-Methoxy-4,4KlimethyMy5-Dihydro-3H-[1,3]bipyridinyl-2,6-dione
A mixture of 5-amino-2-methoxypyride (3.72 g, 30.0 rnmol) and 3,3-dimethylglutaric anhydride (4.26 g, 30.0 mmol) was heated at 175 °C for 7 hours. After cooling down to room temperature the solid material was dissolved in a small amount of dichloromethane and purified by flash column chromatography (Si02l ethyl acetate:heptane (40:60)) yielding the title compound (2.56 g, 34% yield) as a white solid.
1H NMR (300MHz, CDCI3): A/-(6-Methoxy-pyridin-3-yl)-2,2-dimethyl-propionamide hydrochloride
5-Amino-2-methoxypyride (3.72 g, 30.0 mmol), dissolved in a small amount of tefrahydrofu-ran, was added slowly to a solution of 2,2-dimethylpropionyl chloride (3.62 g, 30.0 mmol) in tetrahydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 ml) was added and a thick oil precipitated. The solvent was decanted and the residue was dried under reduced pressure yielding the title compound (5.50 g, 75% yield) as a purple foam. 1H NMR (300MHz, CDCI3): £1.22 (s, 9H), 3.83 (s, 3H), 6.86 (d, 1H), 8.00 (dd, 1H), 8.42 (d, 1H), 9.41 (sf 1 H)( 9.54 (br.s, 1H); HPLC-MS (Method A):, mlz = 209 (M+H); Rt = 2.28 min.
2-Cyclohexyl-N-(6-methoxy-pyridin-3-yl)-acetamide hydrochloride
5-Amino-2-methoxypyride (3.72 g, 30.0. mmol), dissolved in a small amount of tetrahydrofuran, was added slowly to a solution of cyclohexylacetyl chloride (4.82 g, 30.0 mmol) in tetrahydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 ml) was added and the solids were collected by suction yielding the title compound (8.54 g, 100% yield) as a purple solid.
1H NMR (300MHz, DMSO-d6): £0.88-1.04 (m, H), 1.09-1.32 (m, 3H), 1.54-1.82 (m, 6H), 2.18 (dF 2H), 3.84 (s, 3H), 6.85 (d, 1H), 7.98 (dd, 1H), 8.41 (d, 1H), 9.81 (br.s, 1H), 10.10 (s, 1H); HPLC-MS (Method A): mlz = 249 (M+H); Rt = 3.32 min.

N-(6-Hydroxy-pyridIn-3-yl)-benzamide
N-(6-Methoxy-pyridin-3-yI)-benzamide (2.38. g, 10.4 mmol) was dissolved in a mixture of tet-rahydrofuran and diethyl ether. HCI-gas was bubbled into the solution for 5 minutes. More diethyl ether was added and the white precipitate was collected by suction, washed twice with diethyl ether and heated in a kugelrohr apparatus at 180 °C for 0.5 hours. The solid material was crystallised from methanohwater, washed twice with water and dried overnight in a vacuum oven, yielding the title compound (1.19 g, 53% yield) as a grey solid. 1H NMR (300MHz, CDCI3): £6.39 (d, 1H), 7.47-7.61 (m, 3H), 7.18 (dd, 1H), 7.91 (d, 2H), 7.96 (d, 1H); HPLC-MS (Method A): mfz = 215 (M+H); Rt = 1.52 min.
Cyclohexanecarboxylic acid (6-hydroxy-pyridin-3-yl)-amide
Cyclohexanecarboxylic acid (6-methoxy-pyridin-3-yl)-amide hydrochloride (8.12 g, 30.0 mmol) was heated in a kugelrohr apparatus at 190 °C for 25 minutes. After cooling to room temperature the solid material was crystallised from methanol:water, washed twice with water and dried overnight in a vacuum oven, yielding the title compound (3.09 g, 47% yield) as a purple solid.
1H NMR (300MHz, CDCI3): £1.09-1.46 (m, 5H), 1.63 (m. 1H), 1.68-1.80 (m, 4H), 2.23 (m, 1H), 6.33. (d, 1H), 7.44 (dd, 1H), 7.87 (d, 1H), 9.54 (s, 1H), 11.29 (br.s, 1H); HPLC-MS (Method A): m/z= 221 (M+H); Rt = 1.84 min.
6,-Methoxy-4,4-dimethyl-4f5-dihydro-3H-[1,3,]bipyridinyl-2,6-dione (2.56 g, 10.3 mmol) was dissolved in a mixture of tetrahydrofuran and diethyl ether. HCI-gas was bubbled into the solution for 5 minutes. More diethyl ether was added and the white precipitate was collected by suction, washed twice with diethyl ether and heated in a kugelrohr apparatus at 190 °C for 15 minutes yielding the title compound (2.16 g, 89% yield) as a white solid. 1H NMR (300MHz, CDCI3): £1.08 (s, 6H), 2.52 (s, 4H), 6.34 (d, 1H), 7.19 (dd, 1H), 7.31 (d, 1H), 11.42 (br.s, 1H); HPLC-MS (Method A): mlz = 235 (M+H); Rt = 1.32 min.
N-(6-Hydroxy-pyridtn-3-yl)-2,2-dimethyl-propionamide

Under a stream of nitrogen gas /δH-(e-methoxy-pyriclin-S-yl-dimethyl-propionamide hydrochloride (5.50 g, 22.5 mmol) was heated in a round bottom flask at 180 °C for 15 minutes. After cooling to room temperature the solid material was crystallised from a methanol-water mixture, yielding the title compound (1.13 g, 26% yield) as a dark grey solid. 1H NMR (300MHz, CDCI3): £1.18 (s. 9H), 6.32 (d, 1H). 7.53 (dd, 1H), 7.76 (d, 1H), 8.97 (br.s, 1H), 11.30 (br.s, 1H); HPLC-MS (Method A): m/z= 195 (M+H); Rt =1.15 min.
2-Cyclohexyl-N-(6-hydroxy-pyridin-3-yl)-acetamide
2-Cyclohexyl-W-(6-methoxy-pyridin«3-yl)-acetamlde hydrochloride (8.54 g, 30,0 mmol) was heated in a kugelrohr apparatus at 160 °C for 0.5 hours. After cooling to room temperature the solid material was crystallised from a methanol-water mixture, washed twice with water and dried overnight in a vacuum oven, yielding the title compound (4.53 g, 64% yield) as a • grey solid.
1H NMR (300MHz, CDCI3): £0.90-1.38 (m, 5H), 1.60-192 (m, 6H), 2.17 (d, 2H), 6.50 (d, 1H), 7.50 (dd, 1H), 7.97 (d, 1H), 8.80 (br.s, 1H), 11.81 (br.s, 1H); HPLC-MS (Method A): mix-235 (M+H); Rt = 2.29 min.
3-Dimethylamino-2-(4-methoxy-phenoxy)-propenal
Phosphorus oxychloride (18.4 g, 120 mmol) was added to dimethylformamide (8.8 g, 120 mmol), maintaining the temperature below 25 °C by an external ice-bath. Upon.completion of the addition the reaction mixture was heated to 50 °C for 45 minutes and then cooled to room temperature. Chloroform (35 ml) was added and the resulting solution was. brought to reflux. 4-Methoxyphenoxyacetaldehyde diethylacetal (9.61 g, 40.0 mmol) was added in portions. After heating for 3 hours at reflux the solution was cooled to room temperature and poured carefully onto a solution of potassium carbonate (115 g) in water (100 ml). The mixture was cooled in an ice-bath to around room temperature and extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding a brown oil. The residue was heated with ethyl acetate:heptane and decanted, leaving a brown oil. The solvent was removed in vacuo to give a brown oil, which was purified by flash column chromatography (Si02, ethyl acetate) yielding the title compound (3.87 g, 44% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.00 (s, 6H), 3.75 (s, 3H), 6.54. (s, 1H), 7.80 + 7.87 (AB-system, 4H), 6.80 (s, 1H); HPLC-MS (Method A): mlz = 222 (M+H); R, = 1.73 min.

2-(3,4-Dichloro-phenoxy)-3-dimethyIamino-propenal
Phosphorus oxychloride (18.4 g, 120 mmol) was added to dimethylformamide (8.8 g, 120 mmol), maintaining the temperature below 25 °C by an external ice-bath. Upon completion of the addition the reaction mixture was heated to 50 °C for 45 minutes and then cooled to room temperature. Chloroform (35 ml) was added and the resulting solution was brought to reflux. 3,4-Dichlorophenoxyacetaldehyde diethylacetal (9.61 g, 40.0 mmol) was added in portions. After heating for 3 hours at reflux the solution was cooled to room temperature and poured carefully onto a solution of potassium carbonate (115 g) in water (100 ml). The mixture was cooled in an ice-bath to around room temperature and extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding a brown oil, which was purified by flash column chromatography (Si02, ethyl acetate) yielding the title compound (5.38 g, 52% yield) as a brown solid. 1H NMR (300MHz, CDCI3): £3.10 (s, 6H), 6.58 (s, 1H), 6.82
5-(4-Methoxy-phenoxy)-pyrimidin-2-ol
A solution of sodium ethoxide, prepared from sodium (0.80 g, 35.0 mmol), 3-dimethylamino-2-(4-methoxy-phenoxy)-propenal (3.87 g, 17.5 mmol) and urea (2.1 Qg, 35.0 mmol) in etha-nol (25. ml) was heated at reflux for 4 hours. Water (1 ml) was added and heating was.continued for an additional 2 hours. The solution was cooled to room temperature, and neutralised with glacial acetic acid. Most of the solvent was removed by evaporation in vacuo. Water was added and the precipitate was isolated by suction, followed by drying in a vacuum oven, yielding the title compound (0.80 g, 21% yield) as a yellow solid. 1H NMR (300MHzf CDCI3): £3.80 (s, 3H), 6.85-7.95 (AB-system, 4H), 8.12 (s, 2H); HPLC-MS (Method A): m/z= 219 (M+H); Rt = 1.77 min.
5-(3,4-Dichloro-phenoxy)-pyrimidin-2-ol
A solution of sodium ethoxide, prepared from sodium (0.95 g, 41.4 mmol), 2-(3,4-dichloro-phenoxy)-3-dimethylamino-propenal (5.38 g, 20.7 mmol) and urea (2.48 g, 41.4 mmol) in ethanol (25 ml) was heated at 60 °C for 4 hours. Water (1 ml) was added and heating was continued for an additional 2 hours. The solution was cooled to room temperature and neu-

tralised with glacial acetic acid. Most of the solvent was removed by evaporation in vacuo. Water was added and the precipitate was isolated by suction, followed by drying in a vacuum oven, yielding the title compound (0.92 g, 17% yield) as a brown solid. 1H NMR (300MHz, DMSO-d6): £7.08 (dd, 1H), 7.38 (d, 1H), 7.59. (d, 1H), 8.35 (s. 2H), 12.06 (br.s, 1H); HPLC-MS (Method A): m/z = 257 (M+H); Rt = 2.75 min.
5-(2-Nitro-phenyl)-pyrimidin-2-ol
A solution of 3-(dimethylamino)-2-(2-nitrophenyI)acryIaldehyde (2.00 g, 9.08 mmol), urea (0.60 g, 9.99 mmol) and concentrated hydrochloric acid (0.50 ml) in ethanol (25 ml) was heated at 60 °C for 18 hours under a nitrogen atmosphere. An additional aliquot of concentrated hydrochloric acid (0.50 ml) was added followed by heating at 70 °C for 24 hours. The solvent was removed by evaporation under reduced pressure. The residue was crystallised from methanol yielding the title compound (0.35 g, 18% yield) as a yellow solid. 1H NMR (300MHz, DMSO-d6): 57.54 (dd, 1H), 7.62 (dt, 1H), 7.76 (dt, 1H), 8.06 (dd, 1H), 8.29 (s, 2H); HPLC-MS (Method A): m/z = 218 (M+H); Rt = 1.26 min.
N-(6-Hydroxy-pyridin-3-yl)-3,3-dimethyl-butyramide
3f3-Dimethylbutyroyl chloride (4.04 g, 30.0 mmol) was added dropwise to a stirred solution of 5-amino-2-methoxypyridine (3.72 g, 30.0 mmol) in tetrahydrofuran (25 mL). After stirring for 1 hour at room temperature, diethyl ether was added and the solid material was isolated by suction. The A/-(6-methoxy-pyridin-3-yI)-3,3-dimethyl"butyramide hydrochloride (4.13 g, 15.96 mmol) was heated at 180 °C for 15 minutes. After cooling to room temperature the product was dissolved in methanol. Partial evaporation of the solvent yielded the title compound (1.15 g, 35% yield) as a solid.
1H NMR (300MHz, DMSO-cf6): = 100 (s, 9H), 2.12 (s, 2H), 6.38 (d, 1H), 7.44 (dd, 1H), 7.89 (d, 1 H)( 9.59 (s, 1H), 11.42 (br.s, 1H); HPLC-MS (Method A): mfz = 209 (M+H)+; Rt =1.71 min.

Pyridine-2-carboxyIic acid (6-methoxy-pyridin-3-yI)-amide dihydrochloride
5-Amino-2-methoxypyridine (4.40 g, 35.4 mmol), dissolved in a small amount of tetrahydrof u-ran, was added slowly to a stirred solution of pyridine-2-carbonyl chloride hydrochloride (7.12 g, 40.0 mmol) in tetrahydrofuran (75 mL). After stirring overnight at room temperature diethyl ether was added. The solids were isolated by suction, washed with diethyl ether and dried in a vacuum oven at 45 °C, yielding the title compound (7.89 gf 75%). 1H NMR (300MHz, CDCI3): 5= 3.87 (s, 3H), 6.90 (d, 1H)f 7.03 (br.s, 2 HCI + H20), 7.70 (m, 1H), 8.09 (dt, 1H), 8.17 (d, 1H), 8.22 (dd, 1H), 8.68 (d, 1H), 8.73 (m, 1H), 10.82 (s, 1H); HPLC-MS (Method A): mlz = 230 (M+H)+; Rt = 2.45 min and 264 + 266; Rt = 3.15 min.
Pyridine-2-carboxylic acid (6-hydroxy-pyridin-3-yl)-amide hydrochloride
Pyridine-2-carboxylic acid (6-methoxy-pyridin-3-yl)-amide dihydrochloride (0.66 g, 1.99 mmol) was heated at 180 °C for 10 minutes. After cooling to room temperature, the title compound was obtained and used without further purification. HPLC-MS (Method A): mlz = 216 (M+H)+; Rt = 2.14 min.
5-Methoxy-pyrimidin-2-ylamine
Under a nitrogen atmosphere phosphorus pentachloride (21 g, 0.10 mol) was added por-tionwise to 1,1,3-trimethoxyethane (12.0 g, 0.10 mol) with stirring and external cooling (ice-bath). After addition was completed, stirring was continued for an additional 30 minutes at room temperature. Dimethylformamide (22.5. mL) was added by means of a dropping funnel, while the reaction mixture was cooled externally with an ice-bath. After completion of the addition, the reaction mixture was heated at 60 °C for 70 minutes. The reaction mixture was then cooled in an ice-bath and methanol (50 mL) was added dropwise. The resulting solution was added dropwise to a stirred solution of sodium hydroxide (24 g) in methanol (80 mL) while cooling in an ice-bath. Guanldine nitrate (20.0 g, 0.16 mol) and sodium hydroxide (7.0 g, 0.175 mol) were added and the solution was stirred for. 18 hours at room temperature. Water (150 mL) was added and the solution was extracted three times with dichloromethane. The combined organic layers were evaporated in vacuo leaving a brown oil. According to 1H NMR analysis a mixture of the desired product and the intermediate /?-dimethylamine-a-methoxyacroleine was obtained. The mixture was dissolved in methanol (100 mL). Guanidine

nitrate (15.0 g, 0.12 mol) and sodium hydroxide. (5.25 g( 0.13 mol) were added and the reaction mixture was heated at 60 °C for 3 hours, followed by stirring at room temperature for 3 days. Water was. added and the solution was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding the title, compound (5.43 g, 43% yield) as a yellow solid. 1H NMR (300MHz, CDCI3): 8= 3.80 (s, 3H), 5.08 (br.s, 2H), 8.04 (s, 2H); HPLC-MS (Method A): m/z = 126 (M+H)+; Rt = 0.39 min.
1-(5-Methoxy-pyrimidin-2-yl)-4,4-dimethyl-pIperidine-2,6-dione
A mixture of 5-methoxy-pyrimidin-2-ylamine (1.00 g, 7.99 mmol) and 3,3-dimethylglutaric anhydride (1.14 g, 7.99 mmol) was heated at 180 DC for 9 hours. After cooling to room temperature the reaction mixture was dissolved in a small amount of dichloromethane and purified by flash column chromatography (Si02, ethyl acetate:heptane 70:30), yielding the title compound (0.79 g, 40% yield) as a white solid.
1H NMR (300MHz, CDCI3): S= 1.23 (s, 6H), 2.67 (s, 4H), 3.97 (s, 3H), 8.48 (s, 2H); HPLC-MS (Method A): mJz = 250 (M+H)+; Rt = 1.86 min.
1-(5-Hydroxy-pyrimidin-2-yI)-4,4-dimethyl-piperidine-2,6-dione
A mixture of 1-(5-methoxy-pyrimidin-2-yI)-4.4-dimethyl-piperidine-2,6-dione (0.99 g, 3.97 mmol) and pyridine hydrochloride (1.50 g, 7.99 mmol) was heated at 190 °C for 2.5 hours; After cooling to room temperature the reaction mixture was dissolved in a small amount of dichloromethane and filtered over a short pad of silicagel and washed with ethyl acetate. Evaporation of the solvent in vacuo yielded, the title compound (0.60 g, 64 % yield) as a white solid.
1H NMR (300MHz, CDCI3): S= 1.23 (s, 6H), 2.65 (s, 4H), 8.42 (s, 2H), 9.94 (br.s, 1H); HPLC-MS (Method A): mlz = 236 (M+H)+; Rt = 1.53 min.
6-Chloro-N-(6-hydroxy-pyridin-3-yI)-nicotinamide
A solution of 6-chloro-nicotinoyl chloride (0.40 g, 2.27 mmol) and 5-amino-2-hydroxypyridine hydrochloride (0.33 g, 2.25 mmol) in dry tetrahydrofuran (15mL) was stirred at room tempera-

turefor 1 hour. Saturated sodium bicarbonate (aq) was added and the solution was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in a mixture of methanol (10 mL) and aqueous sodium hydroxide (1N, 2 mL). After stirring for 2 hours at room temperature water was added and the solution was extracted with dichloromethane. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound which was used without further purification. HPLC-MS (Method A): mlz = 250 (M+H)+; Rt = 1.52 min.
N-(2r2-Dimethyl-propyl)-6-hydroxy-nicotinamide
A solution of 6-hydroxynicotinic acid (1.39 g, 10.0 mmol), 1-hydroxy-7-azabenztriazole (1.50 g, 11.0 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.11 g, 11.0 mmol) in dimethylformamide (25 mL) was stirred at room temperature for 20 minutes. A solution of 2,2-dimethyipropylamine (0.96 g, 11.0 mmol) and Af,A/-diisopropylethylamine (1.42 g, 11.0 mmol) in a small amount of dimethylformamide was added. Stirring was continued for 0.5 hour at room temperature. Ethyl acetate was added and the reaction mixture was extracted twice with water. The solvent was evaporated in vacuo yielding the title compound, which was used without further purification. HPLC-MS (Method A): mlz = 209 (M+H)+; Rt = 1.86 min.
3-Chloro-6-(3,4-dichloro-phenoxy)-pyridazine
A solution of 3,6-dichloropyridazine (4.47 g, 30.0 mmol), 3,4-dichlorophenol (4.89 g, 30.0 mmol) and potassium hydroxide (1.68 g, 30.0 mmol) in dimethyl sulfoxide (20 mL) was heated at 60 °C overnight The solvent was removed by evaporation in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 50:50). Small amounts of starting material were removed by kugelrohr distillation. Crystallisation from ethyl aceta-te:heptane yielded the title compound (1.74 g, 21 % yield) as a white solid. 1H NMR (300MHz, CDC!3): 6= 7.10 (dd, 1H), 7.20. (d, 1H)f 7.37 (d, 1H), 7.49 (d, 1H), 7.54 (d, 1H); HPLC-MS (Method A): mlz = 275 and 277 (M+H)+; Rt = 4.00 min.

6-(3,4-dichloro-phenoxy)-pyridazin-3-oI
A solution of 3-chloro-6-(3,4-dichloro-phenoxy)-pyridazine (1.74 g, 6.32 mmol) in formic acid (25 mL) was heated at 100 DC for 3 hours. The solvent was removed by evaporation in vacuo yielding the title compound, which was used without further purification. HPLC-MS (Method A): ro/z= 257 (M+Hf; Rt = 3.13 min.
(4-Hydroxy-piperidin-1 -yl)-imidazol-1 -yl-methanone
A solution of 4-hydroxypiperidine (20.0 g, 198 mmol) and N.Af-carbonyldiimidazole (32.06 g, 198 mmol) in tetrahydrofuran (250 mL) was heated overnight at reflux, followed by stirring at room temperature for two days. The solvent was evaporated yielding the title compound, which was used without further purification. HPLC-MS (Method A): mlz = 196 (M+H)+; Rt = 0.39 min.
[4-(tert-Butyl-dimethyl-silanyloxy)-piperidin-1-yI]-imidazoI-1-yl-methanone
tert-Butyldimethylsilyl chloride (30.14 g, 0,20 mol) was added to a stirred solution of (4-hydroxy-piperidin-l-yIHmidazol-1 -yl-methanone (39.05 g, 0.20 mol) in dimethylformamide (200 mL). After stirring for 3 days at room temperature, the solvent was removed by evaporation in vacuo. The residue was redissolved in dichloromethane, extracted twice with water, dried over sodium sulphate, filtered and evaporated In vacuo, yielding the title compound, which was used without further purification.
1H NMR (300MHz, CDCI3): 5 = 0.07 (s, 6H), 0.90 (s, 9H), 1.64 (m, 2H), 1.81 (m, 2H), 3.53-3.74 (m, 4H). 4.06 (m, 1H), 7.07 (m, 1H), 7.18 (m, 1H), 7.86 (m, 1H); HPLC-MS (Method A): m/z = 310 (M+H)+; Rt = 3.40 min.
3-[4-(tert-Butyl-dimethyl-silanyloxy)-piperidine-1 -carbonyI]-1 -methyI-3H-imidazol-1 -ium iodide
Methyl iodide (113.5 g, 0.80 mol) was added to a stirred solution of [4-(fert-butyI-dimethyl-silanyloxy)-piperidin-1-ylI-imidazoI-1-yl-methanone (61.9 g, 0.20 mol) in acetonitrile (400 mL). After stirring overnight at room temperature the solvent was evaporated in vacuo. The resi-

due was washed with ethyl acetaterheptane and dried in a vacuum oven at 45 °C, yielding the title compound (60.92 g, 68% yield over three steps) as a white solid 1H NMR (300MHz, CDCI3): 5 = 0.08 (s, 6H), 0.88 (s, 9H), 1.57 (m, 2H), 1.83 (m, 2H), 3.45 (m, 2H), 3.65 (m, 2H), 3.93 (s, 3H), 4.06 (m, 1H), 7.87 (m, 1H), 8.03 (m( 1H), 9.56 (s, 1H); HPLC-MS (Method A): m/z = 324 (M-l-; Rt = 2.95 min.
4-Chloro-N-(6-hydroxy-pyridin-3-yl)-ben2amide
4-Chlorobenzoyl chloride (1.75 g, 10.0 mmol) was added carefully to a stirred solution of 5-amino-2-methoxypyridine (1.24 g, 10.0 mmol) in dichloromethane (10 mL). After stirring overnight at room temperature, the solvent is evaporated in vacuo and the residue is heated in a pre-heated kugelrohr oven at 200 °C for 5-10 minutes under house-vacuum (around 20 mbar) yielding the title compound, which was. used without further, purification. HPLC-MS (Method A): mlz = 249 (M+H)+; Rt = 2.18 min.
4-Fluoro-N-{6-hydroxy-pyridin-3-yI)-benzamide
Starting from 4-fluorobenzoyl chloride (1.59 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yI)-benzamide yielded the title compound, which was used without further purification. HPLC-MS (Method A): m/z = 233 (M+H)+; Rt = 1.76 min.
N-(6-Hydroxy-pyridin-3-yl)-3-methoxy-benzamide
Starting from 3-methoxybenzoyl chloride (1.71 gF 10.0. mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yI)-benzamide yielded the title compound, which was used without further purification. HPLC-MS (Method A): m/z = 245 (M+H)+; Rt = 1.81 min.

N-(6-Hydroxy-pyridin-3-yl)-4-methoxy-benzamide
Starting from 4-methoxybenzoyl chloride (1.71 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yI)-benzamide yielded the title compound, which was used without further purification. HPLC-MS (Method A): mfz = 245 (M+H)+; Rt = 1.72 min.
N-(6-Hydroxy-pyridin-3-yl)-4-methoxy-benzamide
Starting from 2,4-dichlorobenzoyl chloride (2.10 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification. HPLC-MS (Method A): m/z = 283 (M+H)+; Rt = 2.28 min.
N-(6-Hydroxy-pyridin-3-yl)-4-trifluoromethyI-benzamide
Starting from4-trifluoromethylbenzoyl chloride (2.09 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification. HPLC-MS (Method A): m/z = 283 (M+H)+; Rt = 2.28 min.
Glutaric anhydride (1.14 g, 10.0 mmol) was added to a solution of 5-amino-2-methoxypyridine (1.24 g, 10.0 mmol) in dichloromethane (25 mL). After standing for 1 hour at room temperature, thionyl chloride (5.95 g( 50.0 mmol) was added, followed by heating to reflux for 0.5. hour. The solvent and excess thionyl chloride were evaporated in vacuo, yielding 4-(6-methoxy-pyridin-3-ylcarbamoyl)-butyryl chloride, which was used without further purification.
1H NMR (300MHz, CDCI3): 8 = 1.81 (quintet, 2H), 2.28 (t, 2H), 2.38 (t, 2H), 3.87 (s, 3H), 6.91 (d, 1H), 8.00 (dd, 1H), 8.43 (d, 1H), 10.24 (s, 1H, NH).; HPLC-MS (Method A): m/z = 253 (M+H)+; Rt= 1.94 min. (analysed as methyl ester).

The crude 4-(6-methoxy-pyridin-3"ylcarbamoyl)-butyryl chloride was redissolved in dichloro-methane (25 mL), Thionyl chloride (5.95 g, 50 mmoi) was added and the solution was heated to reflux overnight The solvent and excess thionyl chloride were evaporated in vacuo, yielding B hydrochloride, which was used without further purification.
1H NMR (300MHz, CDCI3): 5 = 2.00 (quintet, 2H), 2.72 (t, 4H), 3.88 (s, 3H), 6.90 (d, 1H), 7.51 (dd, 1 H)f 6.92 (d, 1H), 9.71 (br.s, HCI + H20); HPLC-MS (Method A): m/z = 221 (M+H)+; Rt = 1,38 min.
The crude e-methoxy4,5DIhydro-SH-JtSlbipyridinyl-δHe-dione hydrochloride (2.57 g, 10.0 mmol) was heated in a pre-heated kugerohr oven at 180. °C for 5 minutes. After cooling to room temperature the product was purified by flash column chromatography (Si02l ethyl ace-tate:acetone 25:75), yielding the title compound (0.48 g, 23% yield) as a white solid. 1H NMR (300MHz, CDCI3): = 2.10 (quintet, 2H), 2.81 (t, 4H), 3.53 (br.s, 3H), 7.12 (br.s, 1H), 7.27 (m, 1H), 7.38 (m, 4H), 7.50 (d, 1H), 8.09 (s, 1H); HPLC-MS (Method A): m/z= 340 (M+H)+; Rt = 2.89 min.
1-(6-Methoxy-pyridin-3-yI)-pyrroIidine-2,5-dione
. A mixture of 5-amino-2-methoxypyridine (1.24 g, 10.0 mmol) and succinic anhydride (1.00 g, 10.0 mmol) was heated with a heat gun for 10 minutes. After cooling to room temperature the product was purified by flash column chromatography (Si02,. ethyl acetate:acetone 25:75). Evaporation of the solvent yielded the title compound as a white solid. 1H NMR (300MHz, CDCI3): 5= 2.92 (s, 4H), 3.96 (s, 3H), 6.82 (d, 1H), 7.50 (dd, 1H), 8.11 (d, 1H); HPLC-MS (Method A): mlz = 207 (M+H)+; Rt = 1.26 min.
1-(6-Hydroxy-pyridin-3-yl)-pyrrolidine-2f5-dione
1-(6-Methoxy-pyridin-3-yI)-pyrrolidine-2,5-dione was dissolved in tetrahydrofuran and HCI-gas was bubbled into the solution for 5 minutes. The solvent was evaporated in vacuo and the residue was heated for 10 minutes at 180 °C in a pre-heated kugelrohr oven. After cooling to room temperature, the. residue was purified by flash column chromatography (Si02), yielding the title compound (285 mg, 15% yield over two steps). 1H NMR (400MHz, DMSO-cfe): £= 2.72 (s, 4H), 6.40 (d, 1H), 7.31 (dd, 1H), 7.39 (d, 1H), 11.76 (br.s, 1H, OH); HPLC-MS (Method A): mlz = 193 (M+H)+; Rt = 0.37 min.

2-Methoxy-5-(5-trifluoromethyl-pyridin-2-yloxy)-pyridine
A solution of 5-hydroxy-2-methoxypyridine (1.25 g, 10.0 mmol), 2-chloro-5-trifluoro-methylpyridine (1.82 g, 10.0 mmol) and potassium hydroxide (85% pure, 1.08 g, 10.0 mmol) in dimethyl sulfoxide (25 mL) was heated at 90 °C for 2.5 hours. The solution was cooled to room temperature and poured slowly into water (200 mL). After cooling with an external ice-bath, the precipitate was collected by suction, washed thoroughly with water and dried in a vacuum oven at 45 °C, yielding the title compound (2.56 g, 95% yield). 1H NMR (300MHz, CDCI3): 5= 3.95 (s, 3H), 6.80 (d, 1H). 7.04 (d, 1H), 7.41 (dd, 1H), 7.91 (dd, 1H), 8.03 (d, 1H), 8.40 (d, 1H); HPLC-MS (Method A): mlz = 271 (M+Hf; Rt = 3.88 min.
5-(5-Trifluoromethyl-pyridin-2-yloxy)-pyridin-2-ol
A mixture of 2-methoxy-5-(5-trifluoromethyl-pyridin-2-yloxy)-pyridine (0.28 g, 1.04 mmol) and pyridine hydrochloride (1.00 g, 8.65 mmol) was heated in a kugelrohr oven at 200 °C for 10 minutes. After cooling to room temperature, the reaction mixture is dissolved in dichloro-methane and extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound (180 mg, 68% yield) as a white solid. 1H NMR (300MHz, CDCI3): 8= 6.63 (m, 1H), 7.06 (d, 1H), 7.42 (m, 2H), 7.92 (dd, 1H), 8.42 (d, 1H); HPLC-MS (Method A): mlz = 257 (M+H)+; Rt = 2.32 min.
5-(3,5-Dichloro-pyridin-2-yloxy)-2-methoxy-pyridine
A solution of 5-hydroxy-2-methoxypyridine (1.25 g, 10.0 mmol), 2,3,5-trichloropyridine (1.82 g, 10.0 mmol) and potassium hydroxide (85% pure, 1.08 g, 10.0 mmol) in dimethyl sulfoxide (25 mL) was heated at 90 °C for 1.5 hours. The solution was poured slowly into water (200 mL). The precipitate, was collected by suction, washed thoroughly with water and dried in a vacuum oven at 45 °C, yielding the title compound (2.39 g, 88% yield). 1H NMR (300MHz, CDCi3): = 3.95 (s, 3H), 6.80 (d, 1H), 7.41 (dd, 1H), 7.77 (d, 1H), 7.93 (d, 1H), 8.03 (d, 1H); HPLC-MS (Method A): mlz = 271 (M+H)+; Rt = 4.18 min.

5-(3,5-DichIoro-pyridln-2-yloxy)-pyridin-2-oI
A mixture of 5-(3,5-dichioro-pyridinδH-yloxyVZ-methoxy-pyridine (2.39 g, 8.82 mmol) and pyridine hydrochloride (7.00 g, 60.6 mmol) was heated in a kugelrohr apparatus at 200 °C for 25 minutes. After cooling to room temperature dichloromethane and water were added. The solid material, which was insoluble in dichloromethane and water, was isolated by suction and dried in a vacuum oven at 45 °C, yielding the title compound, which was used without further purification. HPLC-MS (Method A): mlz = 257 (M+H)+; Rt = 2.53 min.
4y4-Dimethyl-3l4y5J6-tetrahydro-2H-[1f3l]bipyridinyl-6l*ol
Under a nitrogen atmosphere lithium aluminium hydride (1.90 g, 50.0 mmol) was added por-tionwise to a stirred suspension of e-methoxy4,4,-dimethyM4,5dihydro-SH-tl,3lbipyridinyl-2,6-dione (2.85 g, 10.0 mmol) in dry diethyl ether (100 mL). After stirring for 3 hours at room temperature, water (1.90 mL), 15% aqueous sodium hydroxide (1.90 mL) and water (5.70 mL) were added respectively. After stirring for 1 hour at room temperature the salts were removed by filtration and washed three times with diethyl ether. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, dichloromethane followed by ethyl acetate/heptane 25/75) yielding the title compound (1.28 g, 58% yield) as a yellow oil.
1H NMR (300MHz, CDCI3): S= 0.98 (s, 6H), 1.53 (m, 4H), 3.03 (m, 4H), 3.89 (s, 3H), 6.67 (d, 1H), 7.30 (dd, 1H), 7.80 (d, 1H); HPLC-MS (Method A): m/z = 221 (M+H)+; Rt = 2.14 min.
4,4-Dimethyl-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6,-ol
A mixture, of 6,-methoxy-4,4-dimethyl-3I4,5,6-tetrahydro-2H-[1,3lbipyridinyl (1.28 g, 5.81 mmol) and pyridine hydrochloride (5.00 g, 43.3 mmol) was heated in a kugelrohr oven at 200 °C for 15 minutes. After cooling to room temperature water was added and the solution was made slightly basic with aqueous 1N sodium hydroxide. The solution was extracted three times with dichloromethane and the combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound (0.86 g, 72% yield). HPLC-MS (Method A): mlz = 207 (M+H)+; Rt = 1.31 min.

Methyl-phenyl-carbamic acid 4-amino-phenyl ester
To a solution of N-Boc protected 4-aminophenol (10 mmol) in CH2Cl2 (50 mL) was added N-methyl-N-phenylcarbamoyl chloride (15 mmol) and DABCO (15 mmol) at room temperature. The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%) and brine. The organic phase was separated, dried (MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 MeOH-CH2CI2 5:95). The purified intermediate was dissolved in CH2CI2(90 mL). Addition of TFA (6 mL) and stirring for 4 h. The reaction mixture was evaporated to dryness and dried in vacuo, at 50 °C overnight producing the title compound in 72% yield as colorless crystals. HPLC-MS: m/z = 243.1 (M+1); Rt = 2.02 min.
Example 1 (General procedure 9)
4-[(1,3-Benzodioxol-5-yI)methyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-
yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-
yloxy)-phenyl chloroformate and 1-piperonylpiperazine, yield 67 %. Recrystallisation from 96
% ethanol gave white crystals, m.p. 239 - 240 °C; HPLC-MS m/z = 502 (M+H), 524 (M+Na),
Rt= 3.3 min.;.; 1H NMR (DMSO-d6): 511.64 (br, 1H, NH), 8.62 - 8.52 (br, 1H, py-H6), 8.31 -
8.19 (m, 1H, py-H4), 7.40 - 7.15 (m, 6H, py-H3 + C6H4+ 1 arom.), 7.15 - 6.93 (m, 2H, arom),
4.53 - 3.96 (br, 4H, CH2 at 4.26 + 2 CH), 3.80 - 2.89 (br, 6H, water at 3.38 + 4C-H); IR (KBr):
v1724(C=0).
Example 2 (General procedure. 1)
Methyl-phenyl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yioxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (36%, white crystals). HPLC-MS m/z = 389.1 (M+1), Rt: 5.13 min.
δH(300MHz; CDCI3): 3.43 (s, 3H), 6.98 (d, 1H, J 8.7), 7.09-7.22 (m, 4H), 7.30-7.34 (m, 1H), 7.35 (d, 2H, J. 7.1), 7.40 (t, 2H, J 6.8), 7.88 (dd, 1H, J 8.7 and 2.3), 8.42 (s, 1H).
Example 3 (General procedure 1)
Methyl-phenyl-carbamic acid 3«(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

The title compound was prepared from 3-(5-trifluoromethyI-pyridin-2δHoxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, dichlormethane) (89%, oil). HPLC-MS m/z = 389.1 (M+1), Rt 5.08 min. δH,(300MHz; DMSO-d6): 3.34 (s, 3H), 7.00-7.15 (m, 3H), 7.27 (t, 2H), 7.35-7.55 (m, 5H), 8.24 (dd,1H),8.58(s, 1H).
Example 4 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(3,5-dichIoro-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3,5-dichloro-pyridin-2-yloxy)-phenol and N-rnethyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (53%, crystals). HPLC-MS m/z = 389.1 (M+1), Rt 5.1 min.
£,(300MHz; CDCI3): 3.43 (s, 3H), 7.07-7.20 (m, 4H), 7.27-7.48 (m, 5H), 7.75 (d, 1H, J 2.2), 7.93(d, 1H.J2.2).
Example 5 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-ylamino)-phenyl ester
The title compound was prepared from4-(5-trifluoromethyl-pyridin-2-ylamino)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC to give the title product (32%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 4,72 min. δH(300MHz; CDCI3): 3.44 (s, 3H), 6.76 (d, 1H), 6.81 (bs, 1H), 7.12 (d, 2H), 7.27-7.45 (m, 6H), 7.63 (dd,1H), 8.42 (bs,1H).
Example 6 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(3,5-dichloro-pyridin-4-yloxy)-phenyl ester
The title compound was prepared from 4-(3,5-dichloro-pyridine-4-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative. HPLC (41%, white crystals). HPLC-MS m/z = 389.1 (M+1), Rt 4.97 min.
c(300MHz; CDCI3): 3.42 (s, 3H), 6.81 (d, 2H, J 9.0), 7.07 (d, 2H, J 7.9), 7.25-7.43 (M, 5H), 8.55 (s, 2H).
Example 7 (General procedure 1)

Methyl-phenyl-carbamic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester
The title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (78%, white crystals). HPLC-MS m/z = 388.0 (M+1), Rt: 5.59 min.
(300MHz; CDCI3): 3.43 (s, 3H), 7.02 (d, 4H, J 8.7), 7.14 (d, 2H, J 8.7), 7.31 (1H, d, J 6.8), 7.35 (d, 2H, J 7.2), 7.41 (t, 2H, J 7.1), 7.55 (d, 2H, J 8.6).
Example 8 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(3-trifluoromethyl-phenoxy)-phenyl ester
The title compound was prepared from 4-(3-trifluoromethyl-phenoxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (73%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 5.37 min.
Example 9 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(2-cyano-5-trifluoromethyl-pyridine-3-yIoxy)-phenyl ester
The title compound was prepared from 4-(2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenol
and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative
HPLC (74%, colourless oil). HPLC-MS m/z = 414.1 (M+1), Rt: 4.8 min.
H(300MHZ; CDCI3): 3.44 (s, 3H), 7.11 (d, 2H, J 9), 7.32-7.1 (m, 3H), 7.32-7.50 (m, 5H), 8.63
(s,1H).
Example 10 (General procedure 1)
Methyl-phenyl-carbamic acid 2-benzenesulfonyl-4-(3-chloro-5-trifluoromethyl-pyridine-2-
yloxy)-phenyl ester
The title compound was prepared from 2-benzenesuIfonyl-4-(3-chIoro-5-trifluoromethyl-
pyridine-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was
purified by preparative HPLC (68%, white crystals). HPLC-MS m/z = 563.1 (M+1), Rt 5.3
min.
(300MHz; CDCl3): 3.44 (s, 3H), 7.20-7.50 (m, 12H), 7.91. (bs, 1H), 8.00 (d, 1H, J 2.3), 8.23
(s, 1H).

Example 11 (General procedure 1) Methyl-phenyl-carbamic acid 4-tert-butoxy-phenyl ester
The title compound was prepared from 4-tert-butoxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad12/25, flash 12, dichlqromethane) followed by a recrystallization from ethanol (41%, crystals). HPLC-MS m/z = 300.3 (M+1), Rt 4.7 min.
c(300MHz; CDCI3): 1.31 (s, 9H), 3.41 (s, 3H), 6.90-7.07 (m, 4H), 7.20-7.28 (m, 1H), 7.32-7.43 (m, 4H).
Example 12 (General procedure 1)
Methyl-phenyl-carbamic acid 3-(4-fluorobenzyI)-4-methyl-2-oxo-2H-chromen-7-yI ester
The title compound was prepared from 3-(4-fluorobenzy[)-7-hydroxy-4-methyl-2H-chromen-2-
one and N-methyl-N-phenylcarbamoyl chloride.
The crude product was of high purity and tested without purification (« 100%, crystals); mp:
185~186°C. HPLC-MS m/z = 418.2 (M+1), Rt: 5.2 min.
ΔH(300MHZ; CDCI3): 2.43 (s, 3H), 3.43 (s, 3H), 6.95 (dt, 2H, J 8.7 and 2.3), 7.10 (m, 2H),
7.21 (dt, 2H, J 7.2 and 2.3), 7.27-7.45 (m, 5H)f 7.58 (d, 1H, J 8.3).
Example 13 (General procedure 1) Methyl-phenyl-carbamic acid 4-phenoxy-phenyl ester
The title compound was prepared from 4-phenoxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (86%, white crystals). HPLC-MS m/z = 320.1 (M+1), Rt: 5.13 min.
ΔH(300MHZ; CDCI3): 3.43 (s, 3H), 6.94-7.02 (m, 4H), 7.08 (t, 2H, J 6.8), 7.04-7.12 (m, 1H), 7.32 (t, 2H, J 7.5), 7.28-7.35 (m, 1H), 7.35-7.45 (m, 4H).
Example 14 (General procedure 1) Methyl-phenyl-carbamic acid 4-(4-chlorobenzoyI)-phenyl ester
The title compound was prepared from 4-(4-chlorobenzoyl)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (90%, white crystals). HPLC-MS m/z = 366.1 (M+1), Rt: 5.19 min.

SH(300MHZ; CDCI3): 3.45 (s, 3H), 7.19-7.37 (m, 4H), 7.40 (t, 2H, J 7.2), 7.37-7.40 (m, 1H), 7.46 (dt, 2H, J 8.7 and. 2T3), 7.73 (dt, 2H, J 8.7 and 2.2), 7.79 (d, 2H, J 8.7).
Example 15 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. Prepared as described in general procedure 1. The crude product was recrystallized (ethanol/water (78%, white crystals). HPLC-MS m/z = 423.1 (M+1), Rt: 5.31 min.
δH(300MHz; CDCI3): 3.43 (s, 3H), 7.10-7.23 (m, 4H), 7.27 (t, 1H, J 6.8), 7.35 (d, 2H, J 7.5), 7.41 (t, 2H, J 7.4), 7.96 (d, 1H, J 1.9), 8.23 (bs, 1H)..
Example 16 (General procedure 1)
Methyl-phenyl-carbamic acid 4-[4-(4-chloro-phenyl)-thiazo!-2-yT|-phenyl ester
The title compound was prepared from 4-[4-(4-chloro-phenyl)-thiazol-2-yi]-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (59%, white crystals). HPLC-MS m/z = 421.1 (M+1), Rt: 5.85 min
ΔH(300MHZ; CDCI3): 3.45 (s, 3H), 7.18-7.25 (m, 2H), 7.27-7.33 (m, 1H), 7.34-7.41 (m, 4H), 7.43 (d, 2H, J 6.8), 7.41-7.46 (m, 1H), 7.92 (dt, 2H, J 8.6 and 2.2), 8.00 (d, 2H, J 8.7).
Example 17 (General procedure 1) Methyl-phenyl-carbamic acid 4-pyrrol-1-yl-phenyl ester
The title compound was prepared from 4-pyrroI-1-yl-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (27%, off-white crystals). HPLC-MS m/z = 293.2 (M+1), Rt: 4.51 min.
ΔH(300MHZ; CDCI3): 3.44 (s, 3H), 6.33 (t, 2H, J 2.2), 7.03 (t, 2H, J 2.2), 7.17 (bd, 2H, J 8.3), 7.29 (d, 1H, J 6.8), 7.31-7.38 (mT 4H), 7.41 (t, 2H, J 6.8).
Example 17a (General procedure 1)
. Methyl-phenyl-carbamic acid 4-imidazoI-1-yl-phenyI ester
The title compound was prepared from 4-imidazo-1-yl-phenol and N-methyl-N-

phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (4%, clear
oil). HPLC-MS m/z = 294.1 (M+1), Rt: 2.25 min.
δH(300MHz; CDCI3): 3.44 (s, 3H), 7.27-7.39 (m, 4H), 7.39-7.50 (m, 5H), 7.53 (bs, 1H)f 8.83
(bs,1H).
Example 18 (General procedure 1)
Methyi-phenyl-carbamic acid 4-(3-chloro-5-trifluoromethyIδHpyridine-2-ylmethyl)-phenyI ester
The title compound was prepared from 4-(3-chloro-5-trifluoromethyI)-pyridine-2-ylmethyl)-
phenol and N-methyl-N-phenylcarbamoyl chloride.
The crude product was recrystallized (ethanol/water) (74%, white crystals). HPLC-MS m/z =
421.1 (M+1), Rt: 5.23 min.
ΔH(300MHZ; CDCI3): 3.40 (s, 3H), 4.33 (s, 2H), 7.03 (d, 2H, J 8.3), 7.20-7.30 (m, 3H), 7.3 (d,
2H, J 7.2), 7.38 (t, 2H, J 7.2), 7.87 (d, 1H, J 1.5), 8.69 (bs, 1H,).
Example 19 (General procedure 1)
Methyi-phenyl-carbamic acid 4-trifluoromethyIsulfanyl-phenyl ester
The title compound was prepared from 4-trifluoromethyIsulfanyl-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (70%, clear oil). HPLC-MS rn/z = 328.0 (M+1), Rt: 5.16 min.
ΔH(300MHZ; CDCI3): 3.42 (s, 3H), 7.19 (d, 2H, J 6.4), 7.26-7.7.37 (m, 3H), 7.41 (t, 2H, J 7.9), 7.63 (d, 2H, J 8.3).
Example 20 (General procedure 1)
Methyi-phenyl-carbamic acid 4-pentafluoromethyloxy-phenyl ester
The title compound was prepared from 4-pentafluoromethyloxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (66%, clear oil). HPLC-MS m/z= 362.0 (M+1), Rt: 5.31 min.
ΔH(300MHZ; CDCI3): 3.42 (s, 3H), 7.10-7.22 (m, 4H), 7.29 (d, 1H, J 7.2), 7.34 (d, 2H, J 7.1), 7.41(t,2H,J7.1).
Example 21 (General procedure 1) Methyi-phenyl-carbamic acid 4-benzyloxy-phenyl ester

The title compound was prepared from 4-benzyloxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (83%, white crystals). HPLC-MS m/z = 334.2 (M+1), Rt: 4.88 min.
δH(300MHz; CDCI3): 3.41 (s, 3H), 5.03 (s, 2H), 6.92 (dt, 2H, J 9.0 and 2.2), 7.02 (d, 2H, J 8.7), 7.26-7.34 (m, 2H), 7.34-7.38 (m, 4H), 7.38-7.44, m, 4H).
Example 22 (General procedure 1) Methyl-phenyl-carbamic acid 4-benzyl-phenyl ester
The title compound was prepared from 4-benzyl-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (56%, white crystals). HPLC-MS m/z = 318.1 (M+1), Rt 5.05 min.
ΔH(300MHZ; CDCI3): 3.41 (s, 3H), 3.95 (s, 2H), 7.02 (d, 2H), 7.12-7.19 (m, 5H), 7.20-7.25 (m, 2H), 7.26-7.28 (m, 1H), 7.28-7.34 (m, 1H), 7.34-7.42 (m, 3H).
Example 23 (General procedure 1) Methyl-phenyl-carbamic acid 4,-cyano-biphenyl-4-yI-ester
The title compound was prepared from 4~hydroxy-4-biphenylcarbonitrile and N-methyl-N-phenylcarbamoyl chloride applying procedure 1. The crude product was recrystallized (ethanol/water) (87%, white crystals). HPLC-MS m/z = 329,2 (M+1), Rt: 4.63 min. δH(300MHz; CDCI3): 3.44 (s, 3H), 7.18-7.26 (m, 2H), 7.26-7.32 (m( 2H), 7.34-7.46 (m;4H), 7.56 (d, 2H), 7.64 (d, 2H), 7.712 (d, 2H).
Example 24 (General procedure 1) Methyl-phenyl-carbamic acid 4'-bromo-biphenyl-4-yl-ester
The title compound was prepared from 4-bromo-4'-hydroxybiphenyl and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol) (72%, white crystals). HPLC-MS m/z = 382.0) (M+1), Rt 5.41 min.
δH300MHz; CDCI3): 3.44. (s, 3H), 7.15-7.23 (d, 2H), 7.26-7.31 (m, 1H), 7.34-7.45 (m, 6H), 7.47.7.57 (m, 4H).
Example 25 (General procedure 1)

Methyl-phenyl-carbamic acid biphenyl-4-yl-ester.
The title compound was prepared from 4-hydroxybiphenyl and N-methyl-N-phenylcarbamoyI
chloride applying. The crude product was recrystallized (ethanol) (75%, white crystals).
HPLC-MS m/z = 304.2 (M+1), Rt: 4.95 min..
ΔH(300MHZ; CDCI3): 3.45 (s, 3H), 7.19 (d, 2H), 7.26-7.37 (m, 2H), 7.37-7.46 (m, 6H), 7.55 (d,
4H).
Example 26 (General procedure 1)
Methyl-phenyl-carbamic acid 4-[3-(4-chlorophenyl)-ureido]-phenyl ester
The title compound was prepared from 4-[3-(4-chloropheny!)-ureidol-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (33%, off-white crystals). HPLC-MS m/z = 396.1 (M+1), Rt: 4.40 min. ΔH(300MHZ; CDCI3): 3.52 (s, 3H), 6.85-7.03 (m, 7H), 7.09 (d, 2H), 7.30-7.50 (m, 6H).
Example 27 (General procedure 1) Methyl-phenyl-carbamic acid 4-(4-nitro-phenoxy)-phenyl ester
The title compound was prepared from 4-(4-nitro-phenoxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (71%, white crystals). HPLC-MS m/z = 365.0 (M+1), Rt: 4.83 min.
ΔH(300MHZ; CDCI3): 3.44 (s, 3H), 7.00 (d, 2H), 7.06 (d, 2H), 7.26-7.32 (m, 1H), 7.33-7.49 (m, 4H), 8.20 (dtf 2H).
Example 28 (General procedure 1) Methyl-phenyl-carbamic acid 4-heptylsulfanyl-phenyl ester
The title compound was prepared from 4-heptylsulfanyl-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (74%, colourless oil, HPLC-MS m/z = 358.2 (M+1), Rt: 6.21 min.
£,(200MHz; CDCI3): 0.87 (t, 3H), 1.15-1.50 (m, 8H), 1.50-1.75 (m, 2H), 2.86 (t, 2H), 3.41 (s, 3H), 7.04 (d, 2H), 7.15-7.50 (m, 7H).
Example 29 (General procedure 1)

Methyl-phenyl-carbamic acid 4-butoxy-phenyl ester.
The title, compound was prepared from 4-butoxy-phenoI and N-methyl-N-phenylcarbamoyI chloride. The crude product was recrystallized from ethanol (22%, white crystals). HPLC-MS m/z = 300.1 (M+1),Rt:5.20.
δH(300MHz; CDCI3): 0.96 (t, 3H), 1.45 (qi, 2H), 1.74 (qi, 2H), 3.41 (s, 3H), 3.92 (t, 2H), 6.84 (d, 2H), 6.99 (d, 2H), 7.25-7.27 (m, 1H), 7.30-7.45 (m, 4H).
Example 30 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(4-chloro-benzenesulfonyl)-phenyl ester
The title compound was prepared from 4-(4-chloro-benzenesulfonyI)-phenol and N-methyl-N-phenylcarbamoyl chloride.. The crude product was subjected to preparative HPLC (46%, colourless oil). HPLC-MS m/z = 402.1(M+1), Rt: 4.65 min.
δH(200MHz; CDCI3): 3.41 (s, 3H), 7.21-7.35 (m, 5H), 7.39 (d, 2H), 7.46 (dt, 2H, 7.84 (dt, 2H) 7,90 (d, 2H).
Example 31 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(4-chloromethyl-thiazol-2-yl)-phenyl ester
The title compound was prepared from 4-(4-chIoromethyl-thiazol-2-yl)-phenol and N-methyl-
N-phenylcarbamoyl chloride. The aqueous phase was adjusted to PH 7.0 (phosphate buffer)
before extraction with ethyl acetate. The crude product was subjected to preparative HPLC
(21 %, white crystals). HPLC-MS m/z = 359.0 (M+1), Rt 4.60.
δH(200MHz; CDCI3): 3.44 (s, 3H), 4.73 (s, 2H), 7.20 (bd, 2H), 7.26-7.48 (m, 6H), 7.92 (bd,
2H).
Example 32 (General procedure 3)
Methyl-phenyl-carbamic acid 4-(4l4-dimethyl-2,6-dioxo-piperidin-1-yl)-phenyl ester
The title product was prepared from 1-(4-hydroxyphenyl)-4.4-dimethylpiperidine-2,6-dione (233 mg, 1.00 mmol)) and 1-methyl-3-(methyl-phenyI-carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol) by applying general procedure 3 (192 mg, 52%, white solid). HPLC-MS mlz = 367 (M+1); Rt = 3.78 min. 1H NMR (300MHz, CDCI3): 51.19 (s, 6H), 2.65 (s, 4H), 3.42 (s, 3H), 7.03 (d, 2H), 7.15-7.43

(m, 7H).
Example 33 (General procedure 3)
c/s-Methyl-phenyl-carbamic acid 4-(1,3-dioxo-octahydro-isoindol-2-yl)-phenyl ester
The title compound (293 mg, 77% yield, white crystals) was prepared from c/s-2-(4-hydroxy-pheny!)hexahydroisoindole-1,3-dione (245 mg, 1.00 mmol) and 1-methyl-3-(methyI-phenyI--carbamoyI-3H-imidazol-1 -ium iodide (343 mgf 1.00 mmol). HPLC-MS mlz = 379 (M+1); Rt = 4.08 min.
1H NMR (300MHz, CDCI3): £1.50 (m, 4H), 1.90. (m, 4H), 3.00 (m, 1H). 3.42 (s, 3H), 7.13-7.44 (m, 9H).
Example 34 (General procedure 3)
Methyl-phenyl-carbamic acid 4-(cyclohexanecarbonyI-amino)-phenyI ester
The title compound (283 mg, 80% yield, white crystals) was prepared from cyclohexanecar-boxylic acid (4-hydroxyphenyI) amide (219 mg, 1.00 mmol) and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazoM-ium iodide (343 mg, 1.00 mmol). HPLC-MS mlz = 353 (M+1); Rt = 4.23 min.
1H NMR (300MHz, CDCI3): 51.27 (m, 3H), 1.52 (m, 2H), 1.70 (m, 1H), 1.76-1.97 (m, 4H), 2.20 (m, 1H)f 3.42 (s, 3H), 7.01 (d, 2H), 7.18 (d, 2H), 7.32-7.50 (m, 7H).
Example 35 (General procedure 3)
Methyl-phenyl-carbamic acid 4-(2-cycIohexyl-acetylamino)-phenyl ester
The title compound (284 mg, 77% yield, white crystals) was prepared from 2-cyclohexyl-W-(4-hydroxy-phenyl)-acetamide (233 mg( 1.00 mmol) and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS mlz- 367 (M+1); Rt = 4.51 min
1H NMR (300MHz, CDCI3): 50.87-1.03 (m, 2H), 1.07-1.38 (m, 3H), 1.60-1.92 (m, 6H), 2.14 (d, 2H), 3.41 (s, 3H), 6.97 (d, 2H), 7.26 (m, 1H), 7.30-7.44 (m, 6H), 7.55 (br.s, 1H, NH);.
Example 36 (Generat procedure 3) cis/trans-Methyl-phenyl-cδHrbamic δH ester

The title compound (353 mg, 86% yield, white crystals) was prepared from cis/trans-4-tert-butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyI)-amide (275 mg, 1.00 mmol) and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imida2ol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS m/z = 409 (M+1); Rt = 5.28 and 5.42 min.
1H NMR (300MHz, CDCI3): £0.82 + 0.86 (2 x s, 9H), 1.03 (m, 2H), 1.23-1.70 (m, 4H), 1.82-2.22 + 2.58 (m, 4H), 3.42 (s, 3H), 7.01 (m, 2H)f 7.26 (m, 1H), 7.31-7.48 (m, 7H, arom. + NH).
Example 37 (General procedure 3)
frans-Methyl-phenyl-carbamic acid 4-[(4-tert-butyl-cyclohexanecarbonyI)-amino]-phenyl ester
The title compound was obtained from c/sδHrans-4-tert-butyI-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide by preparative HPLC (method B). Rt = 5.50 min. 1H NMR (300MHz, CDC!3): £0.85 (s, 9H), 1.03 (m, 3H), 1.52 (m, 2H), 1.88 (m, 2H), 2.01 (m, 2H), 2.12 (tt, J = 12.1, 3.3 Hz, 1H), 3.41 (s, 3H), 7.01 (br.d, 2H), 7.26 (m, 1H), 7.31-7.48 (m, 7H, arom. + NH).
Example 38 (General procedure 3)
c/s-Methyl-phenyl-carbamic acid 4-[(4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester
The title compound was obtained from c/s/?rans-4-tert-butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide by preparative HPLC (method B). Rt = 6.34 min.
Example 39 (General procedure 3)
Methyl-phenyl-carbamic acid 4-(3,3-dimethyl-butyryIamino)-phenyl ester
The title compound (262 mg, 77% yield) was prepared from N-(4-hydroxyphenyO-3,3-dimethyl-butyramide (275 mg, 1.00 mmol) and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLOMS m/z = 341 (M+1); Rt = 4.15 min. 1H NMR (300MHzt CDCI3): £1.07 (s, 9H), 2.16 (s, 2H), 3.43 (s, 3H), 6.98 (d, 2H), 7.26 (m, 1H), 7.32-7.43 (m, 6H), 7.51 (br.s, 1H, NH).
Example 40 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(benzyI)-4-methyl-2-oxo-2H-chromen-7-yl ester


The title compound was prepared from 3-benzyl-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazoH-ium iodide. HPLC-MS m/z = 400 (M+1), Rt 4.90 min.
Example 41 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(3)4-dichloro-benzyI)«4-methyl-2-oxo-2H-chromen-7-yl ester
The title compound was prepared from 3-(3,4-dichIoro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyI-carbamoyl)-1-methyl-3H-imidazoI-1-ium iodide (white solid). HPLC-MS m/z = 468 (M+1), Rt: 5.47 min.
Example 42 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(2-chIoro-6-fluoro-benzyI)-4-methyl-2-oxo-2H-chromen-7-yl
ester
The title compound was prepared from 3-(2-chloro-6-fluoro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyI-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide by applying procedure 3. HPLC-MS m/z = 452 (M+1), Rt; 5.15 min.
Example 43 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(2,6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 468 (M+1), Rt: 5.37 min.
Example 44 (General procedure 3) Melhyl-phenyl-carbamic acid 3-(2,6-dicW yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyl)-6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyI-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 502 (M+1), Rt 5.68 min.
Example 45 (General procedure 3)

Methyl-phenyl-carbamic add 6-chloro-3-(2-chloδH chromen-7-yl ester
The title compound was prepared from 3-(4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyI-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyI)-1-methyl-3H-imidazol-1-ium iodide, HPLC-MS m/z = 480 (M+1), Rt: 5.61 mln.
Example 46 (General procedure 3) Methy!-phenyl-cai±-amic acid ester
The title compound (90 mg, 43% yield, white solid) was prepared from 7-hydroxy-3-(4-methoxy-phenyl)-4-methyl-chromen-2-one (141 mg, 0.50 mmol) and 1-methyl-3-(methyI-phenyl-carbamoyl)-3H-imidazol-1-iurn iodide (175 mg, 0.51 mmol). 1H NMR (300MHz, DMSO-af6): 52.28 (s, 3H), 3.38 (s, 3H)f 3.80 (s, 3H), 7.00 (d, 2H), 7.18-7.33 (m, 5H), 7.40-7.53 (m, 4H), 7.83 (d, 1H); HPLC-MS: m/z = 416 (M+1); Rt = 4.67 min.
Example 47 (General procedure 3)
Methyl-phenyl-carbamic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester
The title compound (120 mg, 52% yield, white solid) was prepared from 7-hydroxy-4-methyl-3-phenyl-chromen-2-one (126 mg, 0.50 mmol) and 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).
1H NMR (300MHz, DMSO-d6): 52.26 (s, 3H), 3.37 (s, 3H), 7.16-7.54 (m, 12H), 7.86 (d, 1H); HPLC-MS: mlz = 386 (M+1); Rt = 4.69 min.
Example 48 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(2T5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-
7-yl ester
The title compound (30 mg, 13% yield, white solid) was prepared from 3-(2,5-dimethoxy-phenyl)-7-hydroxy-4-methyl-chromen-2-one. (156 mg, 0.50 mmol) and 1-methyI-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).
1H NMR (300MHz, CDCI3): 52.21 (s, 3H)f 3.45 (br.s, 3H), 3.72 (s, 3H), 3.79 (s, 3H), 6.74 (m, 1H), 6.92 (m, 2H), 7.12 (br.s, 2H), 7.26-7.46 (m, 5H), 7.63 (d, 1H); HPLC-MS: m/z= 446

(M+1); Rt = 4.60 min.
Example 49 (General procedure 3)
Methyl-phenyl-carbamic acid 3-(3,4-dimethoxy-phenyI)-4-methyl-2-oxo-2H-chromen-7-yl ester.
The title compound (30 mg, 13% yield, oil) was prepared from 3-(3,4-dimethoxy-phenyI)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3-(methyl-phenyI-carbamoyl)-3H-imidazoI-1-ium iodide (175 mg, 0.51 mmol).
1H NMR (300MHz, CDCI3): 52.31 (s, 3H), 3.45 (br.s, 3H), 3.89 (s, 3H), 4.02 (s, 3H), 6.83 (m, 2H), 6.94 (d, 1H), 7.12 (br.s, 2H), 7.27-7.48 (m, 5H), 7.62 (d, 1H); HPLC-MS: m/z = 446 (M+1);Rt = 4.61min.
Example 50 (General procedure 2)
4-Chlor-phenyI-methyI-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title compound was prepared from4-(5-trifluoromethyI-pyridin-2-yloxy)-phenol and 3[(4-chlorophenyI)-methyl-carbamoyl]-1-methyI-3H-imida2ol-1-ium iodide. The crude product was. subjected to flash chromatography (ethyl acetate/heptan, 1:5) (77%, white crystals). HPLC-MS. m/z = 423.1 (M+1), Rt: 5.3 min.
5H(300MHz; CDCI3): 3.42 (s, 3H), 6.99 (d, 1H, J 8.7), 7.10-7.20 (m, 4H), 7.30 (d, 2H, J 8.3), 7.37 (d, 2H, J 8.6), 7.88 (dd, 1H, J 8.7 and 2.2), 8.42 bs, 1H).
Example 51 (General procedure 2)
4-Chlor-phenyl-methyI-carbamic acid 4-(3,5-dichloro-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3l5-dichloro-pyridin-2-yloxy)-phenol and 3-[(4-
r
chlorophenyl)-methyI-carbamoyl]-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (Quad flash 12, dichlormethane (67%). HPLC-MS m/z = 422.9 (M+1), Rt: 5.5 min.
δH(300MHz; CDCI3): 3.41 (s, 3H), 7.20-7.08 (m, 4H), 7.29 (d, 2H, J 9), 7.37 (dd, 2H, J 6.4 and 2.2), 7.76 (df 1H, J 2.3), 7.93 (d, 1H, J 2.3).
Example 52 (General procedure 2)
(4-Chloro-phenyi)-methyl-rarbam

ester
The title compound was prepared from 4-(2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenol and 3-[(4-chlorophenyl)-methyl-C3rbamoyl]-1«methyl-3H-imidazol-1-iurn iodide. The crude product was purified by preparative HPLC (25%). HPLC-MS m/z = 448.2 (M+1), Rt 5.1 min. ΔH(300MHZ; CDCI3): 3.43 (s, 3H), 7.12 (d, 2H, J 9.0), 7.19-7.35 (m, 4H), 7.39 (dd, 2H, J 6.6 and 1.8), 7.36-7.41 (m, 1H), 8.63 (d, 1H, J 0.7).
Example 53 (General procedure1)
Ethyl-phenyl-carbamic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(4-trifluoromethyI-pyridin-2-yloxy)-phenoI and W-
ethyl-A/-phenylcarbamoyI chloride. The crude product was subjected to flash chromatography
(ethyl acetate/heptane, 1:5) (78%, white crystals). HPLC-MS rn/z = 403.2 (M+1), Rt: 5.17
min.
δH(300MHz; CDCI3): 1.25 (t, 3H, J 6.8), 3.83 (q, 2H, J 6.8), 6.98 (d, 1H, J 8.6), 7.12 (m, 4H),
7.32 (d, 2H, J 7.1), 7.32 (m, 1H), 7.41 (t, 2H, J 7.5), 7.87 (dt, 1H, J 8.7 and 2.7), 8.42 (bs,
1H).
Example 54 (General procedure 1)
Ethyl-phenyl-carbamic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester
The title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenol and Af-ethyl-W-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1:5) (77%, white, crystals. HPLC-MS m/z = 402.1 (M+1), Rt: 5.6 min. ΔH(300MHZ; CDCi3): 1.25 (t, 3H, J 7.2), 3.83 (q, 2H, J 7.2), 7.01 (d, 4H, J 8.6) 7.12 (d, 2H, J 8.3), 7.30 (t, 2H, J 6.8), 7.30 (m, 1H), 7.42 (dt, 2H, J 7.5), 7.54 (d, 2H, J 8.6)
Example 55 (General procedure 2)
Benzyl-methyl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3-(benzyl-methyl-carbamoyI)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (ethyl acetate/heptane, (1:5) (69%, colourless oil) HPLC-MS m/z = 403.2 (M+1), Rt 5.11min

300MHz; CDC13): 3,03 (d, 3H, J 8.0), 4.64 (d, 2H, J 24.9), 7.00 (d, 1H), 7.10-7.26 (m, 4H), 7.30-7.50 (m, 5H), 7.88 (dd, 1H), 8.43 (s, 1H).
Example 56 (General procedure 2)
Benzyl-methyl-carbarnic acid 4-(3,5-dichloro pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3,5-dichloro pyridin-2-yloxy)-phenoI and 3-(benzyl-
methyl-carbamoyI)-1 -methyl-3H-imidazol-1-ium iodide.
The crude product was subjected to flash chromatography (Quad flash 12, dichloromethane)
(92%, oil). HPLC-MS m/z = 403.2 (M+1), Rt 5.4 min.
ΔH(300MHZ; CDCI3): 3.02 (d, 3H, J 7.2), 4.60 (d, 2H, J 24.1), 7.05-7.25 (m, 4H), 7.28-7.45
(m, 5H), 7.76 (d, 1H, J 2.3) 7.95 (d, 1H, J J 2.2).
Example 57 (General procedure 2)
tert-Butyi-methyl-carbamic acid 4-(5-trifluoromethyI-pyridin-2-yIoxy)-phenyI ester
The title compound was prepared from 4-(5-trifIuoromethyl-pyridin-2-yloxy)-phenoI and 3-
(tert-Butyi-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was
subjected to preparative HPLC (34%, white crystals). HPLC-MS m/z = 369.1 (M+1), Rt 5.17
min.
δH(300MHz; CDCI3): 1.47 (s, 9H), 3.08 (s, 3H), 6.99 (d, 1H), 7.09-7.20 (m, 4H), 7.87 (dd, 1H),
8.43(bs,1H).
Example 58 (General procedure 2)
Isopropyl-methyl-carbamic acid 4-(5-tr'rfluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3-(isopropyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (ethyl acetate/heptane 1:5) (77%, white crystals). HPLC-MS m/z = 355.1 (M+1), Rt 4.80 min.
δH(300MHz; CDCi3): 1.21 (m, 6H), 2.91 (d, 3H), 4.49 (qi, 1H)f 6.99 (d, 1H), 7.10-7.25 (m, 4H) 7.88 (dd, 1H),8.44(s, 1H).
Example 59 (General procedure 2)
Cyclohexyl-methyl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

The title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenol and 3-(cyclohexyl-methyl-carbamoyI)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to. flash chromatography (ethyl acetate/heptane, 1:5) (80%, white crystals). HPLC-MS m/z = 395.2 (M+1), Rt: 5.7 min.
ΔHH(300MHZ; CDCI3): 1.13 (m, 1H)f 1.50-1.30 ( mf 4H), 1.68 (d, 1Hf J 13.2), 1.75-1.95 (m, 4H), 2.93 (d, 2H, J 12.1), 2.90-3.00 (m, 1H), 4.02 (t, 1H, J 12.1), 6.99 (d, 1H, J 8.7), 7.10-7.17 (, 4H), 7.88 (dd, 1H, J 8.7 and 2.3), 8.44 (s, 1H).
Example 60 (General procedure1)
Dimethyl-carbamic acid 4-(3,5-dichloro pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3,5-dichloro pyridin-2-yloxy)-phenol and dimethyl-carbamoyl chloride. The crude product was purified by preparative HPLC (38%). HPLC-MS m/z = 327.0 (M+1), Rt: 4.7 min. δH(300MHz; CDCI3): 2.92 (s, 3H), 3.05 (s, 3H), 7.10-7.25 (m, 4H), 8.17 (d, 1H), 8.34 (d, 1H).
Example 61 (General procedure 1)
Pyrroiidinel-carboxylic acid 4-(3,5-dichloro-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(3,5-dichloro-pyridine-2-yloxy)-phenol and 1-pyrrolidinecarbamoyl chloride. The crude product was purified by preparative HPLC (64%, white crystals). HPLC-MS m/z = 353.0 (M+1), Rt: 5.00 min.
ΔH(300MHZ; CDCI3): 1.95 (qi, 4H, J 6.4), 3.48 (t, 2H, J 6.4), 3.56 (t, 2H? 6.4), 7.10 (t, 1H, J 2.7), 7.13 (t, 1H, J 2.7), 7.17 (t, 1H, J 2.0), 7.20 (t, 1H, J 2.3), 7.76 (d, 1H, J 2.6), 7.95 (d, 1H J, 2.6).
Example 62 (General procedure 2)
2,3-Dihydro-indole-1-carboxylic acid 4-(5-trjfluoromethyl-pyridin-2-yloxy)-phenyl ester.
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenoI and 3-(2,3-dihydro-indole-1-carbonyI)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to column chromatography( ethyl acetate/heptane, 1:5) (73%, crystals. HPLC-MS m/z = 401.1) (M+1), Rt:5.5 min. δH(300MHz; CDCI3): 3.24 (t, 2H; J 8.4), 4.25 (t, 2H, J 8.4), 7.10 (m, 2H), 7.15-7.35 (m, 6H),

7.90 (dd, 2H, J 8.7 and 2.6), 8.44 (bs, 1H).
Example 63 (General procedure 2)
1,3-Dihydro-isoindole-2-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3-(I.S-dihydro-isoindoIeδHδHarbonylJ-l-methyl-SH-imidazol-l-ium iodide. The crude product was recrystallized (ethanol) («100). HPLC-MS m/z = 401.1 (M+1), Rt 5.1 min. δH(300MHz; CDC!3): 4.85 (s, 2H), 4.95 (s, 2H), 7.01(d, 1H, J 8.69), 7.16 (dt, 2H, J 9.4 and 2.7), 7.22-7.29 (m, 2H), 7.30-7.35 (m, 4H), 7.89 (dd, 1H, J 8.6 and 3.0), 8.45 (m, 1H).
Example 64 (General procedure 2)
Piperidine-1-carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyI ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenoI and 1-methyl-3-(piperidine-1-carbonyI)-3H-imidazol-1-ium iodide. The crude product was recrystallized (ethanol) (45%). HPLC-MS m/z = 367.02 (M+1), Rt 4.9 min. δH(300MHz; CDCI3): 1.65 (bs, 6H), 3.58 (d, 4H, J 21.4), 6.99 (d, 1H, J 8.7), 7.10-7.24 (m, 4H), 7.88 (dd, 1H, J 8.7 and 2.2), 8.44 (bs, 1H).
Example 65 (General procedure 2)
2-Methyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyiidin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-methyl-3-(2-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1:6), (71%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.2 min.
ΔH(300MHZ; CDCI3): 1.26 (d, 3H), 1.40-1.85 (m, 6H), 3.03 (t, 1H), 4.11 (dd, 1H), 4.50-4.65 (m, 1H), 6.95-7.02 (d, 1H)f 7.10-7.20 m, 4H), 7.88 (dd, 1H), 8.43 (bs, 1H).
Example 66 (General procedure 2)
3-Methyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-methyI-3-(3-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was

purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1:6), (75%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.4 min.
δH(300MHz; CDCI3): 0.94 (d, 3H), 1.05-1.20 (m, 1H), 1.50-1.80 (m, 3H), 1.80-1.95 (m, 1H), 2.45-2.75 (dt, 1H)f 2.80-3.00 (m, 1H), 4.00-4.25 (m, 2H), 6.95-7.05 (d, 1H), 7.10-7.25 (m, 4H), 7.88 (dd, 1H), 8.43 (bs, 1H).
Example 67 (General procedure 2)
4-Methyl-piperidine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-methyl-3-(4-methyl-piperidine-1-carbonyl)-3H-imidazoI-1-ium iodide. The crude product was purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1:6), (73%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.4 min.
δH(300MHz; CDCI3): 1.00 (d, 3H), 1.23 (dq, 2H), 1.52-1.65 (m, 1H), 1.70 (d, 2H), 2.75-3.05 (m, 2H), 4.15-4.35 (m, 2H), 6.99 (d, 1H), 7.05-7.20 (m, 4H), 7.88 (dd, 1H), 8.43 (s, 1H).
Example 68 (General procedure 2)
4-Benzyl-piperidine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from4-(5-trifluoromethyI-pyridin-2-yloxy)-phenol and 1-methyl-3-(4-benzyi-pipeiidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was , purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1:6), (72%, white crystals). HPLC-MS m/z = 457.2 (M+1), Rt: 6.0 min.
δH(300MHz; CDCI3): 1.20-1.40 (m, 2H), 1.65-1.85 (m, 3H), 2.59 (d, 2H), 2.70-3.00 (m, 2H), 4.15-4.35 (m, 2H), 6.99. (d, 1H), 7.05-7.22 (m, 6H), 7.22-7.35 (m, 3H), 7.88 (dd, 1H), 8.43 (bs, 1H).
Example 69 (General procedure 2)
3,4-Dihydro-1H-isoquinoline-2-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenoI and 3-(3,4-dihydro-1H-isoquinoIine-2-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was recrystallized (ethanol) (53%). HPLC-MS m/z = 415.2 (M+1), Rt: 5.3 min. δH(300MHz; CDCI3): 2.96 (d, 2H, J 4.9), 3.86 (dt, 2H, J 23.3 and 6.0), 4.79 (d, 2H, J 35.4),

7.00 (d, 1H, J 8.7), 7.10-7.23 (m, 8H), 7.88 (dt, 1H, J 8.7 and 2.1), 8.44 (s, 1H).
Example 70 (General procedure 2) .
3,4-Dihydro-2H-quinoIine-1-carboxylic acid 4-(3,5-dichloro-pyridin-2-yloxy-phenyl ester
The title compound was prepared from 4-(3,5-dichIoro-pyridin-2-yloxy)-phenol and 3-(3,4-dihydro-2H-quinoline-1-carbonyI)"1-methyl-3H-imidazol-1-ium iodide. The crude product was recrystallized (ethano!) (68%). HPLC-MS m/z = 415.2 (M+1), Rt: 5.6 min. ΔH(300MHZ; CDCI3): 2.05 (Qi, 2H, J 6.8), 2.85 (t, 2H, J 6.8), 3.92 (t, 2H, J 6.8), 7.06 (dt, (1H, J 7.4 and 1.1), 7,11-7.19 (m, 4H), 7.21 (t, 1H, J 2.8), 7.24 (t, 1H, J 2.7), 7.77 (d, 1H, J 2.3), 7.75-7.80 (m, 1H), 7.95 (d, 1H, J 2.39).
Example 71 (General procedure 2)
3,4-Dihydn-2H-quinoIine-1 -carboxylic acid 4-(2-cyano-5-trifIuoromethyl-pyridin-3-
y!oxy)-phenyl ester
The title compound was prepared from 4-(2-cyano-5-trifluoromethyi-pyridin-3-yloxy)-phenol and HdihydroδHH-quinoline-l-carbonylδHl-methyl-SH-irnidazoI-l-ium iodide. The crude product was subjected to flash chromatography (Quad flash 12, dichlormethane) (43%, oil). HPLC-MS m/z = 440.2 (M+1), Rt 5.2 min.
ΔH(300MHZ; CDCI3): 2.07 (Qi, 2H, J 6.4), 2.87 (t, 2H, J 6.4), 3.94 (t, 2H, J 6.4), 7.25-7.04 m, 5H), 7.26-7.7.36 (m, 2H), 7.44 (d, 1H, J 1.5), 7.76 (bd, 1H, J 7.2), 8.64 (s, 1H).
Example 72 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxylic acid 3-(3,4-dichIoro-benzyl)-4-methyl-2-oxo-2H-
chromen-7-yl ester
The title compound was prepared from 3-(3,4-dichloro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(3,4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 494 (M+1), Rt 5.86 min.
Example 73 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxylic acid 3-benzyI-4-methyI-2-oxo-2H-chromen-7-yl ester
The title compound was prepared from 3-benzyl-7-hydroxy-4-methyl-2H-chromen-2-one and

Example 74 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxylic acid 3-(2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-
chromen-7-yl ester
The title, compound was prepared from 3-(2-chloro-6-fluoro-benzyI)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(3,4-lihydro-2H-quinoiine-1-carbonyl)-1-methyl-3H-imidazoI-1-ium iodide. HPLC-MS m/z = 478 (M+1), Rt: 5.58 min.
Example 75 (General procedure 3)
3,4-Dihydn-2H-quinoIine-1-carboxyIicacid 3-(2,6-dichloro-benzyl)-4-methyI-2-oxo-2H-chromen-7-yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyI)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(3,4-dihydro-2H-quinoIine-1-carbonyl)-1-methyI-3H-imidazo!-1-ium iodide. HPLC-MS m/z = 494 (M+1), Rt; 5.79 min.
Example 76 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxylic acid 3-(2,6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo-
2H-chromen-7-yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyl)-6-chloro-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(3,4-dihydro-2H-quinoIine-1 -carbonyl)-!-methyl-3H-imidazol-1 -ium iodide. HPLC-MS m/z = 530 (M+1), Rt 6.09 min.
Example 77 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxylic acid 3-(4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-
7-yl ester
The title compound was prepared from 3-(4-fluoro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and SδHSδH-dihydroδHH-quinoline-l-carbonyl)-I-methyl-3H-imidazol-l-ium iodide. HPLC-MS m/z = 444 (M+1), Rt: 5.36 min.

Example 78 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxyiic acid 6-chloro-3-(2-chloro-6-fluoro-benzyl)-4-n-propy-2-oxo-2H-chromen-7-yI ester
The title compound was prepared from 3-(4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyI-2H-chromen-2-one and 3-(3-4-dihydro-2H-quinoIine-1-carbonyl)-1-methyl-3H-imidazoI-1-ium iodide. HPLC-MS m/z = 506 (M+1), Rt 6.01 min.
Example 79 (General procedure 3)
3,4-Dihydro-2H-quinoIine-1 -carboxyiic acid 3-(4-methoxy-phenyI)-4-methyl-2-oxo-2H-
chromen-7-yl ester
The title compound (130 mg, 59% yield, white solid) was prepared from 7-hydroxy-3-(4-methoxy-phenyI)-4-methyI-chromen-2-one (141 mg, 0.50 mmol) and 3-(3,4-dihydro-2H-quinoline-1-carbonyI)-1-methyl-3H-imida2ol-1-ium iodide (188 mg, 0.51 mmol). 1H NMR (300MHz, DMSO-cfe): 52.00 (quintet, 2H), 2.30 (s, 3H), 2.82 (t, 2H), 3.81 (s, 3H), 3.88 (t, 2H), 7.02 (d, 2H), 7.08 (m, 1H), 7.19 (m, 2H), 7.27 (d, 2H), 7.31 (dd, 1H), 7.41 (d, 1H), 7.72 (d, 1H), 7.88 (d, 1H); HPLC-MS: m/z = 442 (M+1); Rt = 5.13 min.
Example 80 (General procedure 3)
3,4-Dihydro-2H-quinoline-1 -carboxyiic acid 4-methyl-2-oxo«3-phenyl-2H-chromen-7-yl
ester
The title compound (150 mg, 73% yield, white solid) was prepared from 7-hydroxy-4-methyl-3-phenyl-chromen-2-one (126 mg, 0.50 mmol) and 3-(3,4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazoI-1-ium iodide (188 mg, 0.51 mmol).
1H NMR (300MHz, DMSO-cfe): £1-99 (quintet, 2H)f 2.28 (s, 3H), 2.82 (t, 2H), 3.88 (t, 2H), 7.08 (m, 1H), 9.19 (m, 2H), 7.33 (m, 3H), 7.46 (m, 4H), 7.74 (d, 1H), 7.90 (d, 1H); HPLC-MS: m/z= 412 (M+1); Rt = 5.14 min.
Example 81 (General procedure 3)
3,4-Dihydro-2tf-quinoiine-1 -carboxyiic acid 3-(2,5-dimethoxy-phenylH-methyl-2-oxo-2H-
chromen-7-yl ester
The title compound (50 mg, 21% yield, white solid) was prepared from 3-(2,5-dimethoxy-
pheny!)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 3-(3,4-dihydro-2H-

quinoline-1 Example 82 (General procedure 3
3,4-Dihydro-2H-quinoIine-1 -carboxylic acid 3-(3,4-dimethoxy-phenyI)-4-methyl-2-oxo-2H-
chromen-7-yl ester
The title compound (50 mg, 21% yield, oil) was prepared from 3-(3,4-dimethoxy-phenyI)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 3-(3,4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide (188 mg, 0.51 mmol).
1H NMR (300MHz, CDCI3): £2.08 (quintet, 2H), 2.33 (s, 3H), 2.88 (t, 2H), 3.89 (s, 3H), 4.03 (s, 3H), 4.06 (t, 2H), 6.65 (m, 2H), 6.96 (d, 1H), 7.05-7.25 (m, 5H), 7.68 (d, 1H), 7.77 (br.d, 1H); HPLC-MS:.m/z=472(M+1); Rt = 5.14min.
Example 83 (General procedure 2)
7-Trifluoromethyl-3l4-dihydro-2H-quinoIine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-
yloxy)-phenyl ester.
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-methyl-3-(7-tnfluoromethyl-3,4-dihydro-2H-quinoline-1 -carbonyl)-3H-imidazol-1 -ium iodide. The crude product was subjected to preparative HPLC (66 %). HPLC-MS m/z: 483.1 (M+1), Rt: 5.87 min.
ΔH(200MHZ; CDCI3): 2.08 (Qi, 2H), 2.90 (t, 2H), 3.98 (t, 2H), 7.03 (d, 1H), 7.1-7.40 (m, 6H), 7.90 (dd, 1H), 8.18 (s, 1H), 8.44 (d, 1H).
Example 84 (General procedure 1)
MorphoIine-4-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compbund was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and mor-pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (37%, white crystals). HPLC-MS m/z = 369.1 (M+1), Rt: 4.3 min.
ΔH(300MHZ; CDCI3): 3.59 (bs, 2H), 3.67 (bs, 2H), 3.76 (m, 4H), 7.01 (d, 1H, J 8.7), 7.12-7.18 (m, 2H), 7.16 (d, 2H, J 3.7), 7.90 (dd, 1H, J 8.7 and 2.6), 8.43 (s, 1H).

Example 85 (General procedure 1) .
Morpho[ine-4-carboxyiic acid 4-(3f5-dichloro-pyridin-4-yIoxy)-phenyI ester
The title compound was prepared from 4-(3,5-dichloro-pyridin-4-yloxy)-phenol and mor-pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (66%, white crystals. HPLC-MS m/z = 368.9 (M+1), Rt: 4.0 min.
δH(300MHz; CDCI3): 3.57 (bs, 2H), 3.65 (bs, 2H) 3.74 (m, 4H), 6.83 (d, 1H, J 9), 6.83 (m, 1H) 7.08 (d, 1H, J 9), 7.08 (m, 1H), 8.56 (s, 2H).
Example 86 (General procedure 1)
Morpholine-4-carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester
The title compound was prepared from 4-(4-trifluoromethyI-phenoxy)-pheno! and morpholine-4-carbonyI chloride. The crude product was purified by preparative HPLC (74%, white crystals). HPLC-MS m/z = 368.1 (M+1), Rt: 4.85 min.
δH(300MHz; CDCI3): 3.59 (bs, 2H), 3.68 (bs, 2H), 3.75 (m, 4H), 7.04 (d, 2H, J 6.4), 7.04 (m, 2H)( 7.14 (d, 1 H, J 9), 7.13 (m, 1H), 7.57 (d, 2H, J 8.3).
Example 87 (General procedure 1) MorphoIine-4-carboxylic acid 4-tert-butoxy-phenyl ester
The title, compound was prepared from 4-(tert-butoxy)-phenoI and 4-morphoIine-carbamoyl chloride. The crude product was recrystallized (ethanol) (69%, crystals); mp: 128.8-129.5°C. HPLC-MS m/z = 280.1 (M+1), Rt: 3.6 min. ΔH(300MHZ; CDCI3): 1.33 (s, 9H,), 3.58 (bs, 2H), 3.66 (bs, 2H), 6.8-7.1 (m, 4H)
Example 88 (General procedure 1)
Morpholine-4-carboxylic acid 4-(3,5-dichloro-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from4-(3l5-dichloro-pyridin-2-yloxy)-phenol and mor-pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (45%, crystals. HPLC-MS m/z = 369.1 (M+1), Rt 4.3 min.
Example 89 (General procedure 1)

Morpholine-4-carboxylic acid 3-(4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yI ester
The title compound was. prepared from 3-(4-fluorobenzyl)-7"hydroxy-4-methyl-2H-chromen-2-one and morpholine-4-carbonyl chloride. The crude product was recrystallized (ethanol) (78%, crystals). HPLC-MS m/z = 398.0 (M+1), Rt: 4.3 min.
δH(200MHz; DMSO-cfe): 2.47 (s, 3H), 3.45 (bs, 2H), 3.56-3.72 (m, 6H), 3.96 (s, 2H), 7.08 (t, 2H), 7.16-7.35 (m, 4H, 7.83 (d, 1H).
Example 90 (General procedure 1)
Morpholine-4-carboxyIic acid 4-(5,7-bis-trifluoromethyl-[1,8]naphthypyridin-2-yloxy)-phenyl
ester
The title compound was prepared from 4-(5,7-bis-trifIuoromethyl-[1,8]naphthypyridin-2-yloxy)-phenol and morpholine-4-carbonyI chloride. The crude product was tested without purification (« 100%). HPLC-MS m/z = 488.0 (M+1), Rt: 5.0 min.
Example 91 (General procedure 3)
Morpholine-4-carboxyIic acid 3-(3)4-dichloro-benzyI)-4-methyi-2-oxo-2H-chromen-7-yi ester
The title compound was prepared from 3-(3,4-dichloro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(morpholine-4-carbonyI)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 448 (M+1), Rt: 4.73 min.
Example 92 (General procedure 3)
Morpholine-4-carbamic acid 3-(benzyl)-4-methyl-2-oxo-2H-chromen-7-yI ester
The title compound was prepared from 3-(benzyl)-7-hydroxy-4-methyI-2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 380 (M+1), Rt: 4.05 min.
Example 93 (General procedure 3)
Morpholine-4-carbamic acid 3-(2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester

The title compound was prepared from 3-(2-chloro-6-fluoro-benzyI)-7-hydroxy-4«methyl-2H-chromen-2-one and 1-methyl-3-(morphoIine-4-carbony!)-3H-imidazol-1-ium iodide, HPLC-MS m/z = 432 (M+1), Rt: 4.36 min.
Example 94 (General procedure 3)
Morpholine-4-carbamic acid SδHδH-dichloro-benzylH-methylδH-oxoδHH-chromen-T-yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyl)-7-hydroxy-4«methyl-2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazoM-ium iodide. HPLC-MS m/z = 448 (M+1), Rt: 4.59 min.
Example 95 (General procedure 3) .
MorphoIine-4-carbamic acid 3-(2,6-dichloro-benzyI)-4-methyl-2-oxo«2H-chromen-7-yl ester
The title compound was prepared from 3-(2,6-dichloro-benzyI)-6-chloro-7-hydroxy-4-methyI-2H-chromen-2-one and 1-methyl-3-(morphoIine-4-carbonyl)-3HHmtdazol-1-ium iodide. HPLC-MS m/z = 484 (M+1), Rt: 4.99 min.
Example 96 (General procedure 3)
MorphoIine-4-carbamic acid The title compound was prepared from 3-(4-fluoro-benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 398 (M+1), Rt: 4.12 min.
Example 97 (General procedure 3) Morpholine-4-carbamicacid 6-chloro-3-(2,6-dichloro-benzyl)-4-n-propy-2-oxo-2H-chromen-7-
yl ester
The title compound was prepared from 3-(4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyl-2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyI)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 460 (M+1), Rt: 4.90 min.
Example 98 (General procedure 3)
Morpholine-4-carboxylic acid 4-methyI-2-oxo-3-phenyl-2H-chromen-7-yl ester

The title compound (75 mg, 41% yield, crystals) was prepared from 7-hydroxy-4-methyI-3-
phenyl-chromen-2-one (126 mg, 0.50 mmol) and 1-methyl-3-(morpholine-4-carbonyl)-3H-
imidazol-1-ium iodide (165 mg, 0.51 mmol).
1H NMR (300MHz, CDCI3): 52.27 (s, 3H), 3.45 (br.s, 2H), 3.62 (br.s, 2H), 3.68 (m, 4H), 7.23
(dd, 1H), 7.32 (m, 3H), 7.43 (m, 3H), 7.87 (d, 1H); HPLC-MS: mlz = 366 (M+1); Rt = 3.79
min.
Example 99 (General procedure 3)
Moipholine-4-carboxylic acid 3-(4-methoxy-phenyI)-4-rnethyl-2-oxo-2H-chromen-7-yI
ester
The title compound (120 mg, 61% yield, crystals) was prepared from 7-hydroxy-3-(4-methoxy-phenyI)-4-methyl-chromen-2-one (141 mg, 0.50 mmol) and 1-methyI-3-(morphoiine-4-carbonyl)-3H-imidazoH-ium iodide (165 mg, 0.51 mmol).
1H NMR (300MHz, DMSO-d6): Example 100 (General procedure 3)
Morpholine-4-carboxylic acid 3-(3,4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester
The title compound (120 mg, 56% yield) was prepared from 3-(3,4-dimethoxy-phenyl)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide (165 mg, 0.51 mmol).
1H NMR (300MHz, DMSO-cf6): 52.29 (s, 3H), 3.46 (br.s, 2H), 3.62 (br.s, 2H), 3.67 (m, 4H), 3.74 (s, 3H), 3.81 (s, 3H), 6.83 (dd, 1H), 6.92 (d, 1H), 7.02 (d, 1H), 7.22 (dd, 1H), 7.30 (d, 1H), 7.85 (d, 1H); HPLC-MS: mlz = 426 (M+1); Rt = 3.80 min.
Example 101 (General procedure 3)
Morpholine-4-carboxyIic acid 3-(2,5-dimethoxy-phenyl)-4-methyI-2-oxo-2H-chromen-7-yl ester

The title compound (120 mg, 56% yield) was prepared from 3-(2,5-dimethoxy-phenyI)-7-hydroxy-4-methyI-chromen-2-one (156 mg, 0.50 mmo!) and 1-methyl-3-(morphoiine-4-carbonyl)-3H-imidazoi-1-ium iodide (165 mg, 0.51 mmol).
1H NMR (300MHz, CDCI3): £2.23 (s, 3H), 3.60 (br.s, 2H), 3.74 (br.s, 2H + s, 3H), 3.80 (m, 4H + s, 3H), 6.73 (m, 1H), 6.92 (m, 2H), 7.13 (m, 2H), 7.64 (d, 1H); HPLC-MSA): m/z= 426 (M+1);Rt = 3.69min.
Example 102 (General procedure 2)
2.6-dimethyl-morpholineδH-rarboxyIicadδH
ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3-
(2f6-dimethyl-morpholine-4-carbonyI)-1"methyI-3H-imidazol-1-ium iodide. The crude product
was purified by preparative HPLC (39%, colorless oil). HPLC-MS m/z = 397.1 (M+1), Rt: 4.64
min.
c5δH(200MHz; CDCI3): 1.22 (s, 3H), 1.25 (s, 3H), 2.50-3.00 (m, 2H), 3.55-3.9 (m, 2H), 4.00-3.30
bd, 2H), 6.90-7.50 (m, 5H), 7.91 (dd, 1H), 8.44 (bs, 1H).
Example 103
Dimethylcarbamic acid benzotriazol-1-yl ester
Example 104
2-Oxo-A/-p-tolylacetamide O-(cyclohexylcarbamoyI)-oxime
Example 105
10,11-Dihydro-dibenzo[a,d]cyclohepten-5-one O-cyclohexylcarbamoyl-oxime
Example 106
l-(4-Chlorophenyl)-non-1-en-3-one O-cyclohexylcarbamoyl-oxime
Example 107
1 ,7,7-Trimethyl-bicyclo[2.2.1]heptan-2-one O-cyclohexylcarbamoyl-oxime
Example 108
1 -(4-Bramophenyl)-6-methyI-hept-1 -en-3-one O-isopropylcarbamoyl-oxime

Example 109
1 -(4-Chloro-phenyI)-non-1 -en-3-one O-isopropylcarbamoyl-oxime
Example 110
4-Bromo-2-(4-chlorobenzyl)-2H-pyra2oIe-3-carbaldehyd6 0-methylrarb
Example 111
1 -(4-BromophenyI)-6-methyl-hept-1 -en-3-one O-propylcarbamoyl-oxlme
Example 112
N-(4-Fluorobenzylcarbamoyloxy)-isobutyrimidoyl chloride
Example 113
N-(2-Hydroxy-2-phenylethylcarbamoyloxy)-isobutyrimidoyl chloride
Example 114
Dimethylcarbamic acid 6-methanesulfonyl-indol-1-yl ester
Example 115
1 -Biphenyl-4-yl-3-methylamino-propenone-cyclohexyl-carbamic acid
Example 116
Dimethylcarbamic acid 4-oxo-1I2,3-benzotriazin-3-yl ester
Example 117
[1-(3"Chloro-5-trifluoromethyl-pyridin"2-yl)-1H-pyrrol-2-yl]-carbamic acid 4-chloro-phenyl ester
Example 118 (General procedure 6) N-MethyI-N-phenyl-5-hexylsulfanyl-3-p-tolyI-[1,2,4]triazole-1-carboxamide
The title compound was prepared from p-toluoyl chloride, 1-bromo-hexane and W-methyl-pheny-lcarbamoyl chloride. The crude product was recrystallized (ethanol/ water); HPLC-MS m/z = 409.2 (M+1), Rt: 6.66 mln.
ΔH(300MHZ; [2H6]DMSO): 0.87 (t, 3H), 1.20-1.35 (mf 4H), 1.35-1.48 (m, 2H), 1.72 (Qi, 2H)f 2.99 (s, 3H), 3.25 (t, 2H), 3.46 (s, 3H), 7.13-7.30 (m, 5H), 7.36 (t, 2H), 7.52 (d, 2H).

Example 119 (General procedure 6) N-Methyl-N-phenethyl-5-ethyI-3-(4-chlorophenyl)-[1,2,4]triazoIe-1 -carboxamide
The title compound was prepared from 4-chlorobenzoyl chloride, 1-bromo-ethane and N-methyl-phenethyl-carbamoyl chloride. The crude product was subjected to preparative HPLC; HPLC-MS m/z = 401.1 (M+1), Rt: 6.17 min.
δH(300MHz; [2H6]DMSO): 1.37 (t, 3H), 2.98 (t, 2H), 3.11 (bs, 3H), 3.23 (Q, 2H), 3.80 (m, 2H), 7.10-7.40 (m, 5H), 7.58 (d, 2H), 8.03 (d, 2H).
Example 120 (General procedure 6) [3-(4-ChlorophenyI)-5-methy!sulfanyI-[1,2,4]triazol-1-yO-morphoIin-4-yl-methanone
The title compound was prepared from 4-chlorobenzoyl chloride, methyl iodide and mor-phoIine-4-carbonyl chloride. The crude product was used without further purification; HPLC-MS m/z = 339.1 (M+1), R5k 4.68 min.
δH(300MHz; [2H6]DMSO): 2.68 (s, 3H), 3.25-3.65 (m, 4H), 3.65-3.85 (m, 4H), 7.58 (d, 2H), 8.03 (d, 2H).
Example 121 (General procedure 6)
N.N-Dimethyl-S-methylsulfanyl-S-naphthalenδH-yl-llδHδHltriazoIe-l-carboxamide The title compound was prepared from 2-naphthoyl chloride, methyl iodide and dimethyl carbamoyl chloride. The crude product was recrystallized from ethanol; HPLC-MS m/z = 313.2 (M+1), Rt: 4.91 min.
δH(300MHz; [2H6]DMSO): 2.74 (s, 3H), 3.18 (s, 6H), 7.53-7.65 (m, 2H), 7.92-8.00 (m, 1H), 8.00-8.17 (m, 3H), 8.62 (s, 1H).
Example 122 (General procedure 6) N,N-Dimethyl-3-(4-chloro-phenyI)-5-ethylsulfanyl-[1,2)4]triazole-1-carboxamide
The title compound was prepared from 2-naphthoyl chloride, methyl iodide and dimethyl carbamoyl chloride. The crude product was recrystallized from ethanol; HPLC-MS m/z = 311.0 (M+1), Rt: 5.13 min. δH(300MHz; [2H6]DMSO): 1.39 (t, 3H), 3.13 (bs, 6H), 3.26 (q, 2H), 7.58 (d, 2H), 8.03 (d, 2H).

Example 123 (General procedure 6) N,N-Dimethyl-3-biphenyI-4-yl-5-methyIsulfanyI-[1,2,4]triazole-1 -carboxamide
The title compound was prepared from 3-biphenylcarbonyl chloride, methyl iodide and dimethyl carbamoyl chloride. The crude product was without further purification; HPLC-MS m/z = 339.1 (M+1), Rt:5.27in.
δH(300MHz; [2H6]DMSO): 2.70 (s, 3H)f 3.16 (bs, 6H), 7.40 (t, 1H), 7.50 (t, 2H)f 7.73 (d, 2H), 7.82 (d,2H), 8.12 (d, 2H).
Example 124
N ,N-Dimethyl-3-(4-chloro-phe
Example 126
N-(4-ChlorophenyI)-3-(4-chlorophenyI)-5-(3-hydroxypropyI)-pyrazoIe-1-carboxamide.
Example 127
5-MorphoIin-4-yI-3-(4-phenoxyphenyl)-pyrazole-1 -carboxylic acid phenethylamide
Example 128
N-Phenyl-4-(4-chlorobenzenesulfonyl)-5-(4-chlorophenyl)-pyrazoie-1-carboxamide
Example 129
N-(3,4-Dichlorophenyl)-2-phenyl-benzimidazole-1-carboxamide
Example 130
Dimethyl-carbamic acid 5-isopropylsuifanyl-4-(3-trifluoromethyl-phenyl)-4H-[1(2,4]triazo!-3-yi ester
Example 131
Dimethyl carbamicacid 1-benzyl-2-oxo-3,5-diphenyl-1,2-dihydro-pyridin-4-yl ester
Example 132
Dimethyl-carbamic acid 7-methoxy-1-methyl-2-oxo-1,2-dihydro-quinoiin-4-yl ester
Example 133
Dimethyl carbamic acid 4-(3-chloro-phenyI)-5-(4-methyI-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl

ester
Example 134 (General procedure 7)
4-Methyl-piperazine-1-carboxyiic acid 4-(5-trifluoromethyl-pyridin-2-yioxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-methylpiperazine. White solid, m.p. 249 - 250 °C (decomp.); HPLC-MS m/z = 458 (M+H), Rt: 3.15 min.; 1H NMR (DMSO-of6): S 11.56 (br. 1H, NH), 8.61 - 8.54 (br, 1H, py-H6)f 8.30 - 8.20 (m, 1H, py-H4), 7.32 - 7.19 (d+ br s, 5H, py-H3 + C6H4), 4.5. - 3.0 (br, 10H, 8 CH + H20), 2.79 (s, 3H, CH3); IR (KBr): v. 1713 (C=0).
Example 135 (General procedure 7)
4-Benzyl-piperazine-1-carboxyIic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenol and 1-benzylpiperazine. White solid, m.p. 229 - 231 °C; HPLC-MS m/z = 458 (M+H), Rt: 3.15 min.; 1H NMR (DMSO-cf6): S 11.17 (br, 1H, NH), 8.61 - 8.54 (br, 1H, py-H6), 8.30 - 8.20. (m,. 1H, py-H4), 7.74 - 7.59 (m, 2H, atom.), 7.52 - 7.41 (m, 3Hf arom.), 7.31 - 7.17 (d+ br s, 5H, py-H3 + C6H4), 4.5 - 4.0 (br, 4H, CH2 + 2 CH), 3.8 - 3.0 (brr 8H, 6 CH + H20); IR (KBr): v 1720 (C=0).
Example 136 (General procedure 7)
4-(2-Hydroxyethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-(2-hydroxyethyl)-piperazine. White solid, m.p. 255 °C; HPLC-MS m/z = 412 (M+H), Rt: 2.12 min.; 1H NMR (DMSO-d6): 8 10.66 (br, 1H, NH), 8.61-8.54 (br, 1H, py-H6), 8.30 - 8.20 (m, 1H, py-H4), 7.32-7.20 (d+ br s, 5H, py-H3 + C6H4), 5.39 (br, 1H, OH)f 4.18 (br, 2H), 3.87 - 3.70 (br t, 2H), 3.70 - 3.02 (br, 8H + water); IR (KBr): v 1714 (C=0).
Example 137 (General procedure 7)
4-(2-Oxo-2-pyrrolidin-1 -yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-
y!oxy)-phenyl ester

The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenoI and 1-(pyrrolidinocart-onylmethyI)-piperazine. White solid, m.p. 224 °C; HPLC-MS m/z = 479 (M+H), Rt: 2.73 min.; 1H NMR (DMSO-cfe): (510.43 (br, 1H, NH), 8.62 - 8.52 (br, 1H, py-H6), 8.31 - 8.20 (m, 1Hf py-H4), 7.34 - 7.18 (d+ br s, 5H( py-H3 + C6H4), 4.40 -3.05 (br, CH2 at 4.26 + water at 3.37 + N-C-H), 2.03 -1.72 (m, 4H, CH2).
Example 138 (General procedure 7)
4-Phenyl-piperazine-1-carboxyIic acid 4-(5-trifluoromethyi-pyridin-2-yIoxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1-phenyl-piperazine (0.5 mmol). The crude product (0.15 g) was partitioned between ethyl acetate (4 ml) and ethyldiisopropylamine (0.04 ml) dissolved in water (4 ml). The organic layer was washed with water (2x5 ml), dried over sodium sulfate. The drying agent was filtered off, and the solvent was removed from the filtrate in vacuo to give the title compound (0.095 g). White crystals, m.p. 117 °C; HPLC-MS m/z = 444 (M+H), Rt: 5.12 min.; 1H NMR (DMSO-cfe): 8 8.61 - 8.55 (br, 1H, py-H6), 8.29 - 8.20 (m, 1H, py-H4), 7.32 -7.14 (m, 7H, py-H3 + C6H4 + 2 arom.), 7.05 - 6.71 (m, 3H, arom.), 3.83 - 3.51 (br, 4H, 2 CH2), 3.28 - 2.99 (m, 4H, 2 CH2).
Example 139 (General procedure 8)
Methyl-phenyl-carbamic acid pyrazol-1-yl ester
The title compound was prepared from 1-hydroxypyrazole and N-methyl-N-phenylcarbamoyl
chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-
heptane) (79%, oil which slowly crystallizes). HPLC-MS m/z = 218.1 (M+1), Rt: 2.82 min. Mp
63-67 °C
ΔH(300MHZ; CDCfe): 3.45 (bs, 3H), 6.28 (s, 3H), 7.30-7.47 (m, 7H).
Example 140 (General procedure 8) Methyl-phenyl-carbamic acid 4-bromo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-bromopyrazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (89%, oil). HPLC-MS. m/z = 298.0 (M+1), Rt 3.77 min. δH(300MHz; CDCI3): 3.44 (bs, 3H), 7.32-7.47 (m, 7H).

Example 141 (General procedure 8)
Methyl-phenyl-carbamic acid 3,4,5-tribromo-pyrazoi-1-yl ester
The title compound was prepared from 1-hydroxy-3,4,5-bromopyrazole and N-methyl-N-
phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad
flash 25, EtOAc-heptane) (93%, colorless crystals). HPLC-MS. m/z = 455.8 (M+1), Rt: 4.88
min. Mp115-119.°C
ΔH(300MHZ; CDCI3): 3.44 (bs, 3H), 7.36-7.48 (m, 5H).
Example 142 (General procedure 8)
Methyl-phenyl-carbamic acid 3-(4-methoxy-phenyl)-pyrazoM-yI ester The title compound was prepared from 1-hydroxy-3-(4-methoxyphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (93%, oil). HPLC-MS m/z = 346.1 (M+Na), Rt: 4.21 min. δH(300MHz; CDCl3): 3.45 (bs, 3H), 3.84 (s, 3H), 6.50 (d, 1H), 6.91 (d, 2H), 7.30-7.48 (m, 6H), 7.70 (d, 2H).
Example 143 (General procedure 8) Methyl-phenyl-carbamic acid imidazol-1-yI ester
The title compound was prepared from 1-hydroxyimidazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (68%, oil). HPLC-MS m/z =218.1 (M+1),Rt: 1.53 min.
ΔH(300MHZ; CDCI3): 3.45 (bs, 3H), 7.00 (bs, 1H), 7.05 (bs, 1H), 7.32-7.49 (m, 5H), 7.55 (bs, 1H).
Example 144 (General procedure 8) Methyl-phenyl-carbamic acid [1,2,3]triazoI-1-yl ester
The title compound was prepared from 1-hydroxy-1,2,3-triazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (80%, oil). HPLC-MS m/z = 219.1 (M+1), Rt: 2.50 min. Mp 105-106 °C.
δH300MHz; CDCI3): 3.46 (bs, 3H), 7.00 (bs, 1H), 7.05 (bs, 1H), 7.31-7.48 (m, 5H), 7.62 (bs, 1H),7.74(s, 1H).
Example 145 (General procedure 7)
4-(lsopropylcarbamoyl-methyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-

yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenol and 1-methyI-piperazine. White solid, m.p. 234 - 235 °C; HPLC-MS m/z = 466 (M+H), Rt: 2.75 min.; 1H NMR (DMSO-cf6): 8 10.50 (br, 1H, NH), 8.66 - 8.54 (br, 2H, NH + py-H6), 8.30 - 8.20 (dd, 1H, py-H4), 7.31 «.. 7.20 (d+ br s,. 5H, py-H3 + C6H4), 4.00 - 3.82 (br m, 5H, methin + 4 CH), 3.70 - 3.09 (br, 9H, 6H + water), 1.11 (d, 6H, CH3).
Example 146 (General procedure 9)
4-Cyclopentyl-piperazine-1-carboxyIic add 4-(5~trifIuoromethyl-pyridin-2-yioxy)-phenyl ester.
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl. chloroformate and 1-cyclopentyl-piperazine. White solid, m.p. 294 - 295 °C; HPLC-MS m/z = 436 (M+H), Rt: 2.92 min.; 1H NMR (DMSO-cf6): 8 11.15 (br, 1H, NH), 8.60 -8.55 (br, 1H, py-H6), 8.29 - 8.20 (m, 1H, py-H4), 7.32 - 7.21 (d+ br s, 5H, py-H3 + C6H4), 4.35 - 3.98 (br, 2H), 3.72 - 3.37 (br m, 5H), 3.29 - 2.97 (br, 2H), 2.12 -1.45 (br m, 8H).
Example 147 (General procedure 9)
4-Butyl-piperazine-1-carboxyiic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-butyl-piperazine. White solid, m.p. 221 - 222 °C; HPLC-MS m/z = 424 (M+H)( Rt: 2.94 min.; 1H NMR (DMSO-cfe): 8 10.86 (br, 1H, NH), 8.60 - 8.55 (br, 1H, py-H6), 8.29 - 8.21 (m, 1H, py-H4), 7.31 - 7.22 (d+ br s, 5H, py-H3 + C6H4), 4.32 -4.03 (br, 2H), 3.65 - 3.44 (br m, 4H), 3,28 - 2.97 (br, 4H), 1.81 -1.60 (br m, 2H), 1.45 - 1.22 (br, 4H), 0.92 (t, 3H, CH3).
Example 148 (General procedure 1) 4-(Methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrro!idin-1-yI ester
The title product was prepared from 4-Hydroxy-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized from

methanol (74%, white crystals).
1H NMR (CDCI3): 8.13 (d, 2H), 7.38-7.55 (m, 6H), 7.30 (t, 1H), 3.37 (s, 3H), 2.89 (s, 4H).
Example 149 (General procedure 10)
4-Hydroxymethyl-piperidine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4-hydroxymethylpiperidine. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1:2 -- 2:1) (78%, light yellow oil). The purified product was crystallized from ethyl acetate/heptane (51%, white solid). HPLC-MS: m/z = 397.1 (M+1); Rt: 4.08 min. 1H NMR (CDCI3): 5 8.44 (s, 1H)T 7.88 (dd, 1H), 7.17 (d, 2H), 7.13 (d, 2H), 7.00 (d, 2H), 4.45-4.20 (bs, 2H), 3.55 (t, 2H), 3.10-2.75 (m, 2H), 1.95-1.65 (m, 3H), 1.47 (t, 1H), 1.29 (dq, 2H).
Example 150 (General procedure 10)
4-Oxo-piperidine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yIoxy)-phenol and 4-piperidone monohydrate. The solvent used was a mixture of dichloromethane and dimethyl-formamide (1:1). The crude product was subjected to preparative HPLC (7%, oil). HPLC-MS: m/z= 381.1 (M+1); Rt: 4.17 min.
Example 151 (General procedure 10)
4-[5-(4-Dimethylamino-phenyl)-1 H-pyrazol-3-yl]-piperidine-1-carboxyIic acid 4-(5-
trifluoromethyl-pyridin-2-yloxy)-phenyL ester
The title product was prepared from 4«(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and NfN-dimethyl-4-[3-(4-piperidinyl)"1H-pyrazoI-5-yI]aniline. The solvent used was a mixture of dichloromethane and dimethylformamide (1:2). The crude product was subjected to. preparative HPLC (4%,oil). HPLC-MS: m/z= 552.2 (M+1); Rt: 4.17 min.
1H NMR (CDCI3): 8.44 (d, 1H), 7.89 (dd, 1H), 7.53 (d, 2H), 7.22-7.10 (m, 4H), 7.00 (d, 1H), 6.73 (d, 2H), 6.27 (s, 1H), 4.45-4.20 (ds, 2H), 3.25-2.95 (m, 3H), 2.88 (s, 6H), 2.15-2.00 (m, 2H), 1.90-1.70 (dq,2H).
Example 152 (General procedure 10)

4-(5-Furan-2-yl-1 H-pyrazoI-3-yl)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and 4-[3-(2-
furyl)-1H-pyrazol-5-yI]piperidine. The solvent used was a mixture of dichioromethane and di-
methylformamide (1:2). The crude product was subjected to preparative HPLC (4%, oil).
HPLC-MS: m/z = 499.1 (M+1); Rt: 4.60 min.
1H NMR (CDCI3): 8.44 (d,1H), 7.89 (dd, 1H), 7.45 ((dd, 1H), 7.24-7.10 (m, 4H), 6.99 (d, 1H),
6.62 (d, 1H), 6.48 (dd, 1H), 6.34 (s, 1H), 4.40-4.25 (bs, 2H), 3.25-2.85 (m, 3H), 2.08 (d, 2H),
1.79(dq,2H).
Example 153 (General procedure 10)
4-BenzyIamino-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-trifIuoromethyl-pyridin)-2-yloxy)-phenol and benzyl-piperidin-4-yl-amine. The crude product was subjected to preparative HPLC (20%, oil). HPLC-MS: mlz = 472.2 (M+1); Rt: 3.34 min.
Example 154 (General procedure 10)
4-(3,4-Dihydro-1 H-isoquinolin-2-ylmethyI)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-
pyridin-2-yloxy)-phenyl ester
The title, product was prepared from 4-5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 2-PiperidinδH-ylmethyl-lδHδHδH-tetrahydro-isoquinoline. The crude product was subjected to preparative HPLC (12%, oil). HPLC-MS: m/z= 512.2 (M+1); Rt: 3.21 min.
Example 155 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(1,3,5-trimethyI-1H-pyrazol-4-ylmethyl)-phenyI ester
The title product was prepared from 4-[(1,3l5-trimethyl-1H-pyrazol-4-yI)methyl]phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (88%, oil). HPLC-MS: mlz = 350.0 (M+1); Rt: 3.52 min. (66% purity).
Example 156 (General procedure 10)
3-Hydroxymethyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI es-

ter
The title product was prepared from 4-(5-trifluorornethyl-pyridin)-2-yloxy)-phenol and 3-hydroxymethyl-piperidine. The crude product was subjected to flash chromatography (Quad Flash 12, ethyl acetate/heptane 1:2). (56%, colourless oil)..HPLC-MS: mlz- 397.1 (M+1); Rt: 4.19 min.
1H NMR (DMSO-d6, 90 °C): 8.37 (sr 1H), 8.00 (dd, 1H), 6.95-7.10 (m, 5H), 4.09 (bsf 1H), 3.91 (dd, 1H), 3.78 (d, 1H), 3.21 (m, 1H), 3.15 (t, 1H), 2.80-2.90 (m, 1H), 2.65 (t, 1H). 1.45-1.70 (mf 3H), 1.25-1.45 (m, 1H)f 1.08 (q, 1H).
Example 157 (General procedure 10)
3-Hydroxy-piperidine-1-carboxylic acid 4-(5-trlfluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyI-pyridin)-2-yIoxy)-phenol and 3-
hydroxy-piperidine. The crude product was subjected to flash chromatography (Quad Flash
12, ethyl acetate/heptane (1:2) (56%, colourless oil). HPLC-MS: m/z= 383.0 (M+1); Rt: 3.98
min.
1H NMR (CDCI3): 8.43 (s, 1H), 7.89 (dd, 1H), 7.23-7.10 (m, 4H), 7.00 (d, 1H), 3.80-4.00 (m,
2H), 3.60-3.80 (m, 1H), 3.25-3.50 (m, 2H), 1.80-2.05 (m, 2H), 1.50-1.70 (m, 3H).
Example 158 (General procedure 10)
4-Benzyl-4-hydroxy-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)"phenol and 4-benzyl-4-hydroxypiperidine. The crude product was subjected to flash chromatography (Quad Rash 12, ethyl acetate/heptane (1:2) (48%, colourless oil). HPLC-MS: mlz- 473.0 (M+1); Rt: 5.04. min.
1H NMR (CDCI3): 8.44 (s, 1H), 7.89 (dd, 1H), 7.28-7.45 (m, 3H), 7.10-7.24 (m, 6H), 7.00 (d, 1H), 4.00-4.14 (bs, 2H), 3.15-3.45 (dt, 2H), 2.81 (s, 2H), 1.66-1.85 (dt, 2H), 1.55-1.65 (m, 2H),1.27(s, 1H).
Example 159 (General procedure 1) Methyl-phenyl-carbamic acid 4-(2-cyano-ethyl)-phenyl ester

The title product was prepared from 3-(4-hydroxyphenyl)proprionitrile and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to. preparative HPLC (11%, colourless oil), HPLC-MS: m/z= 281.2 (M+1); Rt: 3.75 min, purity 80%. 1H NMR (CDCI3): 7.26-7.50 (m, 7H), 7.00-7.15 (m, 2H)f 3.42 (s, 3H), 2.94 (t, 2H), 2.59 8t, 2H).
Example 160 (General procedure 1)
Methyl-phenyl-carbamic acid 4-([1 δHSδHjthiatriazol-S-ylaminoJ-phenyl ester
The title product was prepared from 4-(1,2,3,4-thiatriazol-5-ylamino)phenol and N-methyl-N-
phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (10%,
light brown solid material). HPLC-MS: mlz = 328.0 (M+1); Rt: 3.69. min, purity 81%.
1H NMR (CDCI3): 7.61 (d, 2H), 7.38-7.52 (m, 4H)f 7.19-7.35 (m, 2H)f 6.86-6.95 (m, 1H), 3.35
(s, 3H), 3.33 (s,1H).
Example 161 (General procedure 1)
Methyl-phenyl-carbamic acid 4-pentyI-phenyl ester
The title product was prepared from 4-pentylphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (4%, light brown oil). HPLC-MS: mlz = 298.2 (M+1); Rt: 5.61 min.
1H NMR (CDCI3): 7.31-7.50 (m, 4H), 7.18-7.30 (m, 1H), 7.13 (d, 2H), 7.00 d, 2H), 3.42 (s, 3H), 2.57. (t, 2H), 1.58 (qi, 2H), 1.20-1.40 (m, 4H), 0.87 (t, 3H).
Example 162 (General procedure 1) Methyl-phenyl-carbamic acid 4-(2-methoxy-ethyl)-phenyI ester
The title product was prepared from 4-(2-methoxyethyl)phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (4%, light yellow oil). HPLC-MS: mlz = 286.1 (M+1); Rt: 4.01 min.
1H NMR (CDCI3): 7.30-7.48 (m, 4H), 7.12-7.30 (m, 3H), 7.03 (d, 2H), 3.56 (t, 2H), 3.42 (s, 3H), 3.33 (s, 3H), 2.85 (t, 2H).
Example 163 (General procedure 10)
4-Hydroxy-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and 4-hydroxypjperidine.. The crude product was subjected to flash chromatography (ethyl acetate/heptane (1:1) (48%, light yellow oil). HPLC-MS: mlz = 383.0 (M+1); Rt: 3.88 min* purity 93%.
1H NMR(CDCI3): 8.44 (s, 1H), 7.89 (dd, 1H)f 7.08-7.20 (m, 4H), 6.99 (d, 1H), 3.85-4.10(m, 3H), 3.20-3.45 (m, 2H), 1.85-2.02 (m, 2H), 1.50-1.70 (m, 3H).
Example 164 (General procedure 1) Methyl-phenyl-carbamic acid 4-acetyl-phenyl ester
The title product was prepared from 4'-hydroxyacetophenone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (78%, colourless oil). HPLC-MS: mlz- 270.1 (M+1); Rt: 3.62 min. 1H NMR (CDCI3): 7.96. (d, 2H), 7.15-7.7.48 (m, 7 H), 3.43 (s, 3H), 2.58 (s, 3H).
Example 165 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-4-yl ester
The title product was prepared from 4-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (11%, yellow solid). HPLC-MS: m/z = 229.2 (M+1); Rt: 1.66 min, purity: 67%.
Example 166 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-3-yl ester
The title product was prepared from 3-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (94%, colourless oil). HPLC-MS: mlz = 229.2 (M+1); Rt: 2.54 min.
1H NMR (CDCI3): 10.70 (bs, 1H), 8.50 (d, 1H), 8.45-8.65 (m, 1H), 7.70-7.90 (m, 1H), 7.51 (dd, 1H), 7.42 (d, 2H), 7.34 (d, 2H), 7.28-7.37 (m, 1H), 3.43 (s, 3H).
Example 167 (General procedure 1) Methyl-phenyl-carbamic acid 6-methyl-pyridin-3-yl ester
The title product was prepared from 3-hydroxy-6-methyl-pyridine and N-methyl-N-

phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil). HPLC-MS: mlz = 243.1 (M+1); Rt: 2.24 min.
1H NMR (CDCI3): 10.8 (bs, 1H), 8.54 (m, 1H), 7.76 (m, 1H), 7.26-7.50 (m, 6H), 3.42 (s, 3H), 2.69 (s, 3H).
Example 168 (General procedure 1) Methyl-phenyl-carbamic acid isoquinoIin-1-yl ester
The title product was prepared from and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (15%, colourless oil). HPLC-MS: m/z = 279.1 (M+1); Rt: 3.67 min.
Example 169 (General procedure 1) Methyl-phenyl-carbamic acid 3-phenoxy-phenyl ester
The title product was prepared from 3-phenoxyphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil). HPLC-MS: m/z = 320.1 (M+1); Rt: 5.16 min.
1H NMR (CDCI3): 7.20-7.50 (m, 8 H), 7.11 (t, 1H), 6.95-7.06 (m, 2H), 6.70-6.93 (m, 3H), 3.40 (s, 3H).
Example 170 (General procedure 1) Methyl-phenyl-carbamic acid 3-acetyl-phenyl ester
The title product was prepared from m-hydroxyacetophenone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (62%, colorless oil). HPLC-MS: m/z = 270.1 (M+1); Rt: 3.56 min. 1H NMR (CDCI3): 7.78 (d, 1H), 7.68 (s, 1H), 7.22-7.50 (m, 7H), 3.43 (s, 3H), 2.58 (s, 3H).
Example 171 (General procedure 1)
Methyl-phenyl-carbamic acid 4-acetyl-2-carbamoyl-phenyl ester
The title product was prepared from 5-acetylsalicylamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (87%, white solid). HPLC-MS: mfz= 313.1 (M+1); Rt: 2.51 min.

1H NMR (CDCI3): 8,47 (bs, 1H), 8.08 (dd, 1H), 7.30-7.52 (m, 6H), 6.05 (bs, 1H), 5.38 (bs, 1H), 3.43 (s,3H), 2.61 (s, 3H)..
Example 172 (General procedure 1) Methyl-phenyl-carbamic acid 4-acetyI-3-methyl-phenyl ester
The title product was. prepared from 4,-hydroxy-2l-methyIacetophenone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (76%, white crystals). HPLC-MS: m/z = 284.2 (M+1); Rt: 3.95 min.
1H NMR (CDCI3): 7.72 (d, 1H), 7.22-7.47 (m, 5H), 6.90-7.12 (m, 2H), 3.43 (s, 3H), 2.55 (s, 3H), 2.52 (s, 3H).
Example 173 (General procedure 1) Methyl-phenyl-carbamic acid 1-oxo~indan-4-yl ester
The title product was prepared from 4-hydroxyindanone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (77%, light yellow oil). HPLC-MS: mlz = 282.1 (M+1); Rt: 3.54 min. 1H NMR (CDCI3): 7.61 (d, 1H), 7.27-7.50 (m, 7H), 3.45 (s, 3H)f 3.00 (ds, 2H), 2.67 (t, 2H).
Example 174 (General procedure 1) Methyl-phenyl-carbamic acid benzothiazol-2-yl ester
The title product was prepared from 2-benzothiazolol and N-methyl-N-phenylcarbamoyl chlo- . ride. The crude product was subjected to preparative HPLC. (70%, white crystals). HPLC-MS: m/z 307.1 (M+1); Rt: 4.24 min, purity 85%. 1H NMR (CDCI3): 7.78 (m, 2H), 7.28-7.50 (m, 7H), 3.40-3.70 (d, 3H).
Example 175 (General procedure 1)
Methyl-phenyl-carbamic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester
The title product was prepared from 6-hydroxy-1-tetralone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (49%, colorless oil). HPLC-MS: m/z= 296.2 (M+1); Rt: 3.90 min. 1H NMR (CDCI3): 8.04 (d, 2H), 7.27-7.50 (m, 5H), 7.00-7.10 (m, 2H), 3.42 (s, 3H), Z94 (t,


2H), 2.63 (t, 2H), 2.12 (qu, 2H).
Example 176 (General procedure 1) Methyl-phenyl-carbamic acid benzo[d]isoxazoI-3-yl ester
The title product was prepared from benzo[d]isoxazol-3-ol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (53%, colorless oil). HPLC-MS: mtz= 291.1 (M+23); Rt: 4.05 min.
1H NMR (CDCIs): 7.60-7.75 (m, 1H), 7.49-7.60 (m, 2H), 7.38-7.48 (m, 4H)i 7.28-7.36 (m, 2H), 3.46 (sf 3H).
Example 177 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-2-yI ester
The title product was prepared from 2-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (57%, colorless oil). HPLC-MS: m/z= 229.1 (M+23); Rt: 2.80 min.
1H NMR (CDCI3): 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7.45 (m, 4H), 7.22-7.34 (m, 1H), 7.14-7.21 (t, 1H), 6.99-7.15 (bs, 1H), 3.44 (s, 3H).
Example 178 (General procedure 1)
Methyl-phenyl-carbamic acid 1-(methyl-phenyl-carbamoyl)-1H-benzimidazol-2-yl ester
The title product was prepared from 2-hydroxybenzimidazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (14%, white crystals). HPLC-MS: m/z= 401.2 (M+1); Rt: 3.88 min, purity: 83%. 1H NMR (CDCI3): 7.32 (dd, 2H), 7.24-7.28 (m, 2H), 7.21-7.24 (m, 2H), 7.29 (t, 1H), 7.12-7.19 (mf 5H), 7.09-7.15 m, 2H), 3.28 (s, 6H).
Example 179 (General procedure 1)
Methyl-phenyl-carbamic acid 4-[(pyridine-3-carbonyI)-amino]-phenyl ester
The title product was prepared from N-(4-Hydroxy-phenyl)-nicotinamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (1%, light yellow crystals). HPLC-MS: m/z= 348.1 (M+1); R<: min.>
Example 180 (General procedure 11)
4-Py!ToIidin-1-yl-piperidine«1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4«(5-trifluoromethy!-pyridin}-2-yloxy)-phenoI and 4-(1-pyrrolidinyI)piperidine. The crude product was used without further purification (68%, white solid). HPLC-MS: rnlz = 436.2 (M+1); Rt: 2.98 min. 1H NMR (DMSO-d6): 10.90 (bs, 1H), 8.57 (s, 1H), 8.24 (dd, 1H), 7.15-7.30 (m, 5H), 4.00-
4.40 (m, 2H), 3.45-3.60 (m, 2H), 2.75-3.25 (m, 4H), 2.05-2.25 (d, 2H), 1.80-2.05 (m, 5H),
1.60-1.80 (m,2H).
Example 181 (General procedure 12)
Methyl-o-tolyl-carbamic acid 4-(trifluoromethyI-pyridin-2-yioxy)-phenyI ester
The title product was prepared from 4-(5-trifluoromethyI-pyridin)»2-yloxy)-phenoI and N-methyl-o-toluidine. The crude product was subjected to preparative HPLC (51%, colorless oil). HPLC-MS: mlz = 403.2 (M+1); Rt: 4.89 min.
1H NMR (CDCI3): 8.40 (s, 1H), 7.87 (dd, 1H), 7.05-7.18 (m, 4H), 6.96 (d, 1H), 3.30 (s, 3H), 2.36 (s, 3H).
Example 182 (General procedure 12)
Methyl-pyridin-2-yl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 2-(methylamino)pyridine. The crude product was subjected to preparative HPLC (55%, white solid). HPLC-MS: rnlz =390.1 (M+1); Rt: 4.31 min.
Example 183 (General procedure 12)
Methyl-m-tolyl-carbamic add 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5«trifluoromethyl-pyridin)-2-yloxy)-phenol and N-methyl-m-toluidine. The crude product was subjected to preparative HPLC (51%, colorless oil). HPLC-MS: rnlz = 403.2 (M+1); Rt: 4.98 min. 1H NMR (CDCI3): 8.42 (s, 1H), 7.88 (dd, 1H), 7.28 (d, 1H), 7.05-7.25 (m, 7H), 6.97 (d, 1H),
3.41 (sf 3H), 2.38 (s, 3H).

Example 184 (General procedure 12)
(3-ChIoro-phenyI)-methyI-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yioxy)-phenoI and 3-chloro-N-methyianiline. The crude product was subjected to preparative HPLC (54%, colorless oil). HPLC-MS: mlz = 423.1 (M+1); R{: 5.07 min.
1H NMR (CDCI3): 8.42 (m, 1H), 7.88 (dd, 1H), 7.39 (m( 1H), 7.33 (t, 1H), 7.22-7.30 (m, 2H), 7.10-7.7.22 (m, 4H), 6.99 (d, 1H), 3.43 (s, 3H).
Example 185 (General procedure 12)
Methyl-p-tolyi-carbamic acid 4-(5-trifluoromethyl -pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and N-methyl-p-toluidine. The crude product was subjected to preparative HPLC (54%, white solid). HPLC-MS: m/z= 403.2 (M+1); Rt: 4.99 min.
1H NMR (CDCI3): 8.42 (s, 1H), 7.87 (dd, 1H), 7.05-7.30 (m, 8H), 6.98 (d, 1H), 3.40 (s, 3H)f 2.36 (s, 3H).
Example 186 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(3-pyridin-3-yl-acryloyl)-phenyl ester
The title product was prepared from 1-(4-hydroxy-phenyI)-3-pyridin-3-yl-prop-2-en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (56%, off-white solid). HPLC-MS: mlz = 359.0 (M+1); Rt: 3.27 min. 1H NMR (CDCI3): 8.87 (d, 1H), 8.65 (dd, 1H), 8.03 (d, 2H), 7.97 (dt, 1H), 7.79 (d, 1H), 7.57 (d, 1H), 7.33-7.47 (m, 5H), 7.27-7.33 (m, 3H), 3.44 (s, 3H), 3.49 (t, 1H), 1.21 (t, 1H).
Example 187 (General procedure 14)
Methyl-phenyl-carbamic add 4-[3-(3I4!5-trimethoxy-phenyl)-acryloyl]-phenyl ester
The title product was prepared from 1-(4-hydroxyphenyl)-3-(3,4,5-trimethoxyphenyI)prop-2-en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (82%, yellow solid). HPLC-MS: mlz = 448.2 (M+1); Rt: 4.61 min. 1H NMR (CDCU): 8.01 (d, 2H), 7.70 (d, 1H), 7.33-7.47 (m, 4H), 7.28-7.33 (m, 2H), 6.86 (s,

IH), 3.92 (s, 6H), 3.90 (s, 3H), 3.45 (s, 3H).
Example 188 (General procedure 14)
Methyl-phenyl-carbamic acid 4-diethylcarbamoyl-2-methoxy-phenyl ester
The title product was prepared from N,N-diethyI-4-hydroxy-3-methoxy-benzamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (58%, colorless oil). HPLC-MS: mlz= 357.1 (M+1); Rt: 3.64 min.
1H NMR (CDCI3): 7.34-7.44 (m, 4H), 7.21-7.28 (m, 1H), 7.03-7.09 (d, 1H), 6.99 (d, 1H), 6.90 (dd, 1H)f 3.87 (s, 3H), 3.15-3.65 (bs, 4H), 3.43 (s, 3H), 1.05-1.35 (m, 6H).
Example 189 (General procedure 14) Methyl-phenyl-carbamic acid 3-phenylcarbamoyi-phenyl ester
The title product was prepared from 3-hydroxy-N-phenyl-benzamide and N-methyl-N-
phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (54%,
white solid). HPLC-MS: m/z= 347.2 (M+1); Rt: 4.01 min.
1H NMR (CDCl3): 7.76 (s, 1H), 7.68 (d, 1H), 7.58-7.65 (m, 3H), 7.27-7.51 (m, 8H), 7.15 (t,
1H),3.44(s,3H).
Example 190 (General procedure 14) Methyl-phenyl-carbamic acid quinolin-7-yl ester
The title product was prepared from 7-hydroxyquinoline and N-methyi-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (28%, white solid). HPLC-MS: m/z= 279.1 (M+1); R*: 2.55 min.
1H NMR (CDCI3): 8.93 (dd, 1H), 8.18 (d, 1H), 7.83-7.86 (m, 1H), 7,82 (d, 1H), 7.35-7.50 (m, 6H), 7.27-7.32 (m, 1H)r 3.47 (s, 1H).
Example 191 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(4-methyl-piperazine-1-carbonyl)-phenyl ester
The title product was prepared from 1-(4-hydroxybenzoyl)-4-methyl-piperazine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (22%, colorless oil). HPLC-MS: m/z = 354.1 (M+1); Rt: 2.07 min.

1H NMR (CDCI3): 7.37-7.49 (m, 4H), 7.28-7.37 (m, 3H), 7.16-7.25 (m, 2H), 4.60-4.00 (bs( 2H), 3.43 (s, 3H), 3.35-3.90 (bs, 4H), 2.82 (s, 3H) 2.55-2.90 (bs, 2H).
Example 192 (General procedure 14) Methyl-phenyi-carbamic acid 3-acetylamino-phenyI ester
The title product was prepared from 3-acetamidophenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (66%, white solid). HPLC-MS: m/z= 285.1 (M+1); Rt: 3.09 min.
1H NMR (CDC!3): 7.40-7.49 (m, 1H), 7.31-7.40 (m, 5H), 7.25-7.30 (m, 1H), 7.22 (d, 1H), 7.14 (d, 1H)f 6-84 (bd, 1H), 3.42 (s, 3H), 2.10 (s, 3H).
Example 193 (General procedure 14) Methyl-phenyi-carbamic acid 4-benzoyI-phenyI ester
The title product was prepared from (4-hydroxy-phenyI)-phenyI-methanone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (36%, colorless oil). HPLC-MS: m/z = 332.2 (M+1); Rt: 4.42 min.
1H NMR (CDCI3): 7.75-7.85 (m, 4H), 7.58 (tt, 1H), 7.33-7.52 (m, 6H), 7.27-7.32 (m, 1H), 7.18-7.25 (m, 2H), 3.44 (s, 3H).
Example 194 (General procedure 14) Methyl-phenyi-carbamic acid biphenyl-3-yl ester
The title product was prepared from 3-phenyiphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (52%, colorless oil). HPLC-MS: mtz = 304.2 (M+1); Rt: 4.75 min. 1H NMR (CDCI3): 7.52-7.67 (m, 2H), 7.22-7.52 (m, 11H), 7.03-7.22 (m, 1H), 3.45 (s, 3H).
Example 195 (General procedure 14) Methyl-phenyi-carbamic add 1H-indol-4-yl ester
The title product was prepared from 4-hydroxyindole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (48%T off-white solid). HPLC-MS; m/z = 267.1 (M+1); Rt: 3.57 min.

1H NMR (CDC!3): 8.20 (els, 1H), 7.36-7.50 (m, 4H), 7.17-7.35 (m, 2H), 7.08-7.17 (m, 2H), 6.94 (d, 1H), 6.44 (s, 1H), 3.48 (s, 3H).
Example 196 (General procedure 14)
Methyl-phenyl-carbamic acid 5,6,7,8-tetrahydro-naphthalen-1-yI ester
The title product was prepared from 5,6,7,8-tetrahydro-1-naphthol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (42%, colorless oil). HPLC-MS: m/z= 282.1 (M+1); Rt: 4.77 min.
1H NMR (CDCI3): 7.33-7.45 (m, 4H), 7.22-7.32 (m, 1H), 7.02-7.13 (t, 1H), 6.82-7.96 (m, 2H), 3.42 (s, 3H), 2.70-2.82 (m, 2H), 2.50-2.65 (m, 2H), 1.62-1.83 (m, 4H).
Example 197 (General procedure 14)
Methyl-phenyl-carbamic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-1-y] ester
The title product was prepared from 5,6J,8-tetrahydro-1-naphthoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (60%, colorless oil). HPLC-MS: m/z= 296.1 (M+1); Rt: 3.81 min.
1H NMR (CDCI3): 7.91 (dd, 1H), 7.21-7.50 (m, 7H), 3.44 (s, 3H), 2.60-2.93 (bs, 2H), 2.62 (t, 2H), 2.02-2.20 (m, 2H).
Example 198 (General procedure 14)
Methyl-phenyl-carbamic acid 1,3-dioxo-1,3-dihydro-isobenzofuran-4-yi ester
The title product was prepared from 4-hydroxy-isobenzofuran-1,3-dione and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: ro/z= 298.1 (M+1); Rt: 2.58 min, purity: 85%. 1H NMR (CDCI3): 7.90 (d, 1H), 7.48-7.62 (m, 2H), 7.28-7.45 (m, 5H), 3.38 (s, 3H).
Example 199 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-chloro-pyridin-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to column chromatography (ethyl acetate/heptane (1:5) (85%, white solid). HPLC-MS: mJz= 355.1 (M+1); R*: 4.56 min.

1H NMR (CDCI3): 8.10 (df 1H), 7.62 (dd, 1H), 7.31-7.44 (m, 4H), 7.25-7.30 (m, 1H), 7.05-7.20 (m, 4H), 6.84 (d, 1H), 3.43 (s, 3H).
Example 200 (General procedure. 14)
(3-Fluoro-pheny()-methyl-carbamic acid 4-(5-tnTIuoromethyl-pyridin-2-yIoxy)-phenyl ester
The title product was prepared from 4-(5"TrifIuoromethyI-pyridin-2-yloxy)-phenoI and 3-fluoro-N-methylaniline. The crude product was subjected to preparative HPLC (31%, white solid). HPLC-MS: m/z = 407.0 (M+1); Rt: 4.93 min.
1H NMR (CDC!3): 8.42 (s, 1H), 7.88 (dd, 1H), 7.36 (q, 1H), 7.07-7.24 (m, 6H), 7.00 (d, 1H), 7.92-7.05 (rn, 1H), 3.44 (s, 3H).
Example 201 (General procedure 11)
4-Benzy!-piperazine-1-carboxylic acid 4-(5-chloro~pyridin-2-yIoxy)-phenyI ester
The title product was prepared from 4-(5-chIoro-pyridin-2-yIoxy)-phenol and 1-benzylpiperazine. The title product precipitated from the reaction mixture and was collected by filtration (88%, off-white solid). HPLC-MS: rnlz = 424.1 (M+1); Rt: 2.91 min. 1H NMR (CDCI3): 13.86 (bs, 1H)f 8.11 (d, 1H)f 7.60-7.70 (m, 3H), 7.45-7.55 (m, 3H), 7.05-7.20 (m, 4H), 6.98 (d? 1H), 4.26-4.40 (m, 2H, 4.15-4.25 (m, 2H), 3.38-3.53 (m, 2H)f 3.60-4.15 (m, 2H), 2.72-2.92 (m, 2H).
Example 202 (General procedure 11)
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yIoxy)-phenyI ester
The title product was prepared from 4~(5-chloro-pyridin-2-yloxy)-phenoI and (3-pyridylmethyl)piperazine. The title product precipitated from the reaction mixture and was collected by filtration and recrystallized from ethanol (35%, off-white solid). HPLC-MS: mfz = 425.2 (M+1); Rt: 2.39 min.
1H NMR (CDCI3): 13.00-14.50 (bs, 1H), 8.72 (d, 2H)( 8.50 (bs, 1H), 8.11 (d, 1H), 7.64 (dd, 1H), 7.56 (bs, 1H), 7.06-7.14 (m, 4H)f 6.88 (df 1H), 3.6-4.4 (m, 6H), 2.70-3.50 (m, 4H).
Example 203 (General procedure 14)
4-Hydroxymethyl-piperidine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-pheny( ester

The title product was prepared from 4-(5-chloro-pyridin-2-ylaxy)-phenoI and 4-hydroxymethyl-piperidine..The crude product was subjected to column chromatography (ethylacetate/heptane, 1:1) (75%, colorless oil). HPLC-MS: mlz- 363.1 (M+1); Rt: 3.58 min. 1H. NMR (CDCIs): 8.12 (d, 1H), 7.64 (dd, 1H), 7.05-7.24 (m, 4H), 6.85 (d, 1H), 4.33 (ds, 2H), 3.56 (t, 2H), 2.75-3.10 (m, 2H), 1.69-1.95 (m, 3H)f 1.56 (s, 1H), 1.19-1.45 (m, 2H).
Example 204 (General procedure 1) Methyl-phenyl-carbamic acid 4-morpholin-4-yl-phenyl ester
The title product was prepared from and 4-morpholin-4-yI-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was extracted with dichloromethane from citric acid (5%). The combined organic phases were evaporated and the product crystallized from ethanol (22%, crystals). HPLC-MS: m/z= 313.2 (M+1); Rt: 3.75 min.
1H NMR (DMSO-d6): 7.35-7.50 (m, 4H), 7.22-7.32 (m, 1H), 7.00 (d, 2H), 6.92 (d, 2H), 3.72 (t, 4H), 3.32 (s, 3H), 3.05 (t, 4H).
Example 205 (General procedure 1)
1,4-Dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4-piperidone ethylene ketal. The crude product was extracted with dichloromethane from citric acid (5%). The. combined organic phases were evaporated and the product crystallized from ethanol (61 %, crystals). HPLC-MS: mlz = 425.2 (M+1); Rt: 4.45 min.
Example 206 (General procedure 14)
The title product was prepared from 2-(4-hydroxy-phenyl)-indan-1,3-dione and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (1%, oil). HPLC-MS: mlz* 372.1 (M+1); Rt: 4.80 min.
Example 207 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(5,6-dichloro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-phenyI ester
The title product was prepared from 5,6-dichloro-2-(4-hydroxy-phenyI)-isoindole-1,3-dione

and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (2%,). HPLC-MS: m/z = 441.1 (M+1); Rt: 5.00 min.
Example 208 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(2-phenoxy~acetylamino)~phenyI ester
The title product was prepared from N-(4-hydroxy-phenyI)-2-phenoxy-acetamide and N-methyl-N-phenylcarbarnoyl chloride. The crude product was purified by preparative HPLC (54%, oil). HPLC-MS: m/z= 277.2 (M+1); Rt: 4.19 min.
Example 209 (Genera! procedure 14)
Methyl-phenyl-carbamic acid 4-[2-(4-chloro-phenyI)-ethyI]-phenyl ester
The title product was prepared from 4-(4-chlorophenethyI)-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (57%, white crystals). HPLC-MS: m/z= 366.1 (M+1); Rt: 5.58 min.
1H NMR (CDCI3): 7.31-7.45 (m, 4H)( 7.17-7.30 (m, 3H)f 6.96-7.12 (m, 6H), 3.41 (s, 3H), 2.85 (s, 4H).
Example 210 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester
The title product was prepared from pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (41%,)- HPLC-MS: m/z= 348.1 (M+1); Rt: 4.00 min.
1H NMR (CDCI3): 7.32-7.47 (m, 4H), 7.24-7.31 (m, 3H), 7.10-7.23 (m, 4H), 7.79 (d, 2H), 3.41 (m, 6H).
Example 211 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[methyI-(thiophene-2-carbonyl)-amino]-phenyl ester
The title product was prepared from thiophene-2-carboxylic acid (4-hydroxy-phenyI)-methyl-amide and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (16%, oil). HPLC-MS: mlz = 367.2 (M+1); Rt: 3.97 min.

Example 212 (General procedure 14) Methyl-phenyl-carbamic acid 4-butyrylamino-phenyl ester
The title product was prepared from4'-hydroxybutyraniIide and N-methyl-N-phenylcarbarnoyl chloride. The crude product was subjected to preparative HPLC (60%, white solid). HPLC-MS: mlz = 313.2 (M+1); R*: 3.58 min.
Example 213 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(4,6-dimethyI-pyrimidin-2-yIsulfanyl)-phenyl ester
The title product was prepared from 4-(4,6-dimethyIpyrimidin-2-ylsuIfanyI)-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (59%, white solid). HPLC-MS: m/z = 366.1 (M+1); Rt: 4.50 min.
1H NMR (CDCI3): 7.59 (d, 2H), 7.32-7.45 (m, 4H), 7.23-7.31 (m, 1H), 7.16 (d, 2H), 6.68 (s, 1H), 3.43 (s,1H), 2.32.
Example 214 (General procedure 14) Methyl-phenyl-carbamic acid 4-methanesulfonyl-phenyl ester
The title product was prepared from 4-methyIsulfonylphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: mlz = 306.1 (M+1); Rt: 3.22 min.
Example 215 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[2-(3-oxo-1,2,3,4-tetrahydro-quinoxalin-2-yl)-acetylamino]-
phenyl ester
The title product was prepared from N-(4-hydroxyphenyl)-2-(3-oxo-1,2,3,4-tetrahydro-2-quinoxalinyf)acetamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (20%, yellow solid). HPLC-MS: m/z= 431.2 (M+1); Rt: 3.55. min.
Example 216 (General procedure 14) Methyl-phenyl-carbamic acid 4-phenylacetyl-phenyl ester

The title product was prepared from benzyl 4-hydroxyphenyi ketone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (68%, light yellow oil). HPLC-MS: mtz = 431.2 (M+1); Rt: 3.55 min.
Example 217 (General procedure 12)
4-Benzoyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and 4-benzoylpiperidine (29%, white solid). HPLC-MS: m/z= 471.3 (M+1); Rt: 5.12 min.
Example 218 (General procedure 11)
[1,4]BipiperidinyI-1'-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yIoxy)-phenoI and 4-piperidinopiperidine. The crude product was filtered from the reaction mixture and washed with diethyl ether to give the title product (50%, off-white solid).. HPLC-MS: mlz = 450.1 (M+1); Rt: 3.12 min.
Example 219 (General procedure 12)
4-(2-Oxo-2,3-dihydro-benzimidazol-1 -yl)-piperidine-1 -carboxylic acid 4-(5-trif luoromethyl-
pyridin-2-y!oxy)-phenyl ester
The title product was prepared from 4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenol and 1-piperidin-4-yl-1,3-dihydro-benzoimidazof-2-one (44%, oil). HPLC-MS: m/z = 499.1 (M+1); Rt: 4.35 min.
1H NMR (CDCI3): 10.15 (s, 1H), 8.44 (s, 1H), 7.90 (dd, 1H), 7.23 (t, 1H), 7.13-7.20 (m, 4H), 7.06-7.13 (m. 2H), 7.02 (d, 1H), 4.40-4.70 (m, 3H), 2.95-3.30 (m, 2H), 2.40-2.63 (m, 2H), 1.86 (d,2H).
Example 220 (General procedure 12)
3-Diethylcarbamoyl-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester
The title product was prepared from 4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenol and N,N-diethylnipecotamide (56%, oil). HPLC-MS: /77/z = 466.1 (M+1); R*: 4.51 min.

Example 221 (Genera! procedure 12)
4-CarbamoyI-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-TrlfluoromethyI-pyridin«2-yloxy)-phenol and piperidine-4-carboxylic acid amide. The crude product was subjected to preparative HPLC (47%, white solid). HPLC-MS: m/z= 410.2 (M+1); Rt: 3.45 min.
Example 222 (Genera! procedure 12)
3-CarbamoyI-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-TrifIuoromethyl-pyridin-2-yloxy)-phenoI and nipeco-tamide. The crude product was purified by preparative HPLC (60%, white solid). HPLC-MS: m/z= 410.2 (M+1); Rt: 3.45 min.
Example 223 (General procedure 14)
Methyl-phenyl-carbamic acid 4-{[4-(methyl-phenyl-carbamoyloxy)-2-oxo-1,2-dihydro-
quinoline-3-carbonyI]-amino}-phenyi ester
The title product was prepared from 4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid (4-hydroxyphenyI)-amide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (6.6%, oil). HPLC-MS: m/z= 563.2 (M+1); Rt: 4.46 min. 1H NMR (CDC!3): 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7.45 (m, 4H), 7.22-7.34 (m, 1H), 7.14-7.21 (t, 1H)f 6.99-7.15 (bs, 1H), 3.44 (s, 3H).
Example 224 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[(4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carbonyl)-amino]-
phenyl ester
The title product was prepared from 4-hydroxy-2-oxo-1,2-dihydro-quinoIine-3-carboxylic acid (4-hydroxy-phenyI)-amide and N-methyl-N-phenylcarbamoyl chloride (5%,). HPLC-MS: mlz-430.1 (M+1); Rt: 4.80 min, purity: 70%.
Example 225 (General procedure 14) Methyl-phenyl-carbamic acid 4-(4-hydroxy-benzyI)-phenyl ester

The title compound was prepared from 4,4'-dihydroxydiphenylmethane and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative. HPLC (21 %, white crystals which turn red after standing). HPLC-MS: m/z = 324.2 (M+1); Rt: 4.21 min.
Example 226. (General procedure 13)
Methyl-phenyl-carbamic acid 4-(4-trifluoromethyl-benzylcarbamoyI)-phenyl ester
The title product was prepared from 4-(methyI-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 4-trifluoromethyl-benzylamine (94%, white crystals). HPLC-MS: mfz = 429.2 (M+1); R{: 4.35 min.
Example 227 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(butyl-methyI-carbamoyI)-phenyI ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yI ester and /7-butyI-methyl-amine. The crude product was subjected to preparative HPLC (20%, oil). HPLC-MS: mlz= 341.2 (M+1); Rt: 3.96 min.
Example 228 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(methyl-phenethyl-carbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and methyl-phenethyl-amine. The crude product was subjected to preparative HPLC (29.%, oil). HPLC-MS: m/z=389.2 (M+1); Rt: 4.15 min.
Example 229 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(pyridin-2-ylmethyl)-carbamoyl]-phenyI ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 2-aminomethyIpyridine. The crude product was used without further purification (57%, oil). HPLC-MS: m!z= 362.2 (M+1); R,: 2.43 min. 1H NMR (MeOH-cU): 8.50 (d, 1H), 7.92 (d, 2H), 7.83 (dt, 1H), 7.38-7.50 (m, 5H), 7.26-7.37 (m, 2H), 7.15-7.26 (m, 2H), 4.69 (s, 2H), 3.41 (s, 3H).
Example 230 (General procedure 13)

Methyl-phenyl-carbamic acid 4-(2"pyridin-2-yl-ethylcarbamoyI)-phenyI ester
The title product was prepared from 4-(methyl-phenyI-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and 2-aminoethylpyridine. The crude product was used without further purification (26%, oil). HPLC-MS: m/z = 376.2 (M+1); Rt: 2.25 min.
1H NMR (MeOH-d4): 8.51 (d, 1H), 7.87 (dt, 1H), 7.78 (d, 2H), 7.33-7.50 m, 6H)t 7.25-7.33 (m, 1H), 7.18 (d, 2H), 3.74 (t, 2H), 3.41 (bs, 3H), 3.13 (t. 2H).
Example 231 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(2-phenylamino-ethylcarbamoy!)-phenyI ester
The title product was prepared from 4-(methy!-phenyi-carbamoy!oxy)-benzoic acid 2,5-dioxo-pyrrolidine 1-yI ester and N-phenylethylenediamine. The crude product was used without further purification (80%, off-white foam). HPLC-MS: m/z = 390.2 (M+1); Rt: 3.51 min. 1H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7.48 (m, 4H), 7.22-7.34 (m, 1H), 7.15-7.22 (d, 2H), 7.10. (t, 2H), 6.69 (d, 2H), 6.62 (t, 1H), 3.72 (t, 2H), 3.57 (t, 2H), 3.40 (s, 3H), 3.20 (s, 1H).
Example 232 (General procedure 13)
Methyl-phenyl-carbamic acid 4-{3-methyl-butyIcarbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and /so-amylamine. The crude product was used without further purification (95%, oil). HPLC-MS: m/z = 341.2 (M+1); Rt: 3.99 min.
1H NMR (MeOH-d4): 7,82 (d, 2H), 7.36-7.50 (m, 4H), 7.26-7.35 (m, 1H)( 7.15-7.24 (d. 2H), 3.34-3.46 (mr 5H), 1.67 (sept, 1H), 1.50 (q, 2H), 0.96 (d, 6H).
Example 233 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(3,3~dimethyI-butylcarbamoyI)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic add 2,5-dioxo-pyrrolidin-1-yl ester and 3,3-dimethylbutylamine. The crude product was used without further purification(88%, oil). HPLC-MS: m/z= 355.1 (M+1); Rt: 3.10 min. 1H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7.50 (m, 4H), 7.25-7.35 (m, 1H), 7.15-7.25 (d, 2H), 3.33-3.47 (m, 5H), 1.49-1.57 (m, 2H), 0.97 (s, 9H).

Example 234 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(tetrahydro-furan-2-ylmethyl)-carbamoy!]-phenyl ester
The title product was prepared from 4-(methyI-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and C-(tetrahydro-furan-2-yI)methyIamine. The crude product wasused without further purification (86%, oil). HPLC-MS: m/z = (M+1);Rt: min. 1H NMR (MeOH-d*): 7.84 (d, 2H), 7.35-7.50 (mf 4H), 7.25-7.35 (m, 1H), 7.12-7.25 (d, 2H), 4.10 (qui, 1H)f 3.87 (q, 1H), 3.68-3.82 (m, 1H), 3.41 (s, 3H), 3.35-3.54 (m, 2H), 1.82-2.10 (m, 3H), 1.58-1.72 (m,1H).
Example 235 (General procedure 13)
Methyl-phenyl-carbamic acid 4-cyclohexylcarbamoyI-phenyl ester
The title product was prepared from 4-(methyl-phenyi-carbarnoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and cyclohexylamine. The crude product was used without further purification (79%, off-white crystals). HPLC-MS: m/z= 353.2 (M+1); Rt: 3.98 min. 1H NMR (MeOH-d4): 8.18 (df 1H), 7.85 (d, 2H), 7.36-7.52 (m, 4H), 7.25-7.33 (m, 1H), 7.20 (d, 2H), 3.74 (m, 1H), 1.77-1.88 (m, 2H), 1.65-1.77 (m, 2H), 1.60 (d, 1H), 1.24-1.40 (m, 4H), 1-07-1.23 (m, 1H).
Example 236 (General procedure 13)
Methyl-phenyl-carbamic acid 4-cyclopropylcarbamoyl-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and cyclopropylamine. The crude product was used without further purification (97%, oil). HPLC-MS: m/z= 311.2 (M+1); Rt: 3.21 min.
1H NMR (MeOH-d4): 7.81 (d, 2H), 7.36-7.50 (m, 4H), 7.25-7.36 (m, 1H), 7:18 (d, 2H), 3.40 (bs, 3H), 2.78-2.87 (m, 1H), 0.75-0.85 (m, 2H)f 0.57-0.65 (m, 2H).
Example 237 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(cyc!ohexylmethyI-carbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and C-cyclohexyl-methylamine. The crude product was used without further purification (84%, oil). HPLC-MS: m/z= 367.3 (M+1); Rt:4.28 min.

1H NMR (MeOH-d4):7.81 (d, 2H)f 7.36-7.49 (m, 4H), 7.25-7.32 (m, 1H), 7.19 (d, 2H), 3.40 (bs, 3H), 3.20 (d, 2H), 1.55-1.82 (m, 5H), 1.13-1.35 (m, 4H), 0.90-1.10 (m, 2H).
Example 238
Methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester
A solution of 2-hydroxy-5-nitropyridine (1.40 g, 10.0 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (3.43 g, 10.0 mmol) and triethylamine (0.42 ml, 10.0 mmol) in acetonitrile (25 ml) was heated at 50 °C for 5 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:-heptane (25:75)) followed by crystallisation from ethyl acetate:heptane yielding the title compound (1.13 g, 41% yield) as a white solid.
1H NMR (300MHz, CDCl3): 53.44 (br.s, 3H), 7.17 (br.d, 1H), 7.27-7.45 (mf 5H), 8.49 (br.d, 1H), 9.19 (br.s, 1H); HPLC-MS (Method A): mlz = 296 (M+Na); Rt = 3.45 min.
Example 239
Methyl-phenyl-carbamic acid pyrimidin-2-yl ester
A solution of 2-hydroxypyrimidine hydrochloride (0.40 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.83 ml, 6.00 mmol) in acetonitrile (15 ml) was stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02l ethyl acetate) followed by crystallisation from ethyl acetaterheptane yielding the title compound (0.08 gf 12% yield) as a white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 7.14-7.31 (m, 2H), 7.39 (m, 4H), 8.68 (d, 2H); HPLC-MS (Method A): mlz = 252 (M+Na); Rt = 2.32 min.
Example 240
Methyl-phenyl-carbamic acid 7-chloro-quinolin-4-yl ester
A solution of 7-chloro-4-hydroxyquinoline (0.54 g, 3.00 mmol), 1-methyI-3-(methyl-phenyI-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for. 18 hours. The solvent was evaporated in vacuo and the. residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (40:60)) yielding the title compound (0.87 g, 93% yield) as a colourless

oil which solidified upon standing.
1H NMR (300MHz, CDCI3): £3.47 (br.s, 3H), 7.28-7.58 (m, 8H), 8.05 (br.s, 1H), 8.85 HPLC-MS (Method A): mlz = 313 (M+H); Rt = 3.79 min.
Example 241
Methyl-phenyl-carbamic acid quinoIin-4-yI ester
A mixture of 4-hydroxyquinoIine (0.44 g, 3.00 mmol)), 1-methy!-3-(methyl-phenyI-carbamoyI)-3H-imida2ol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3,00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.75 g, 90% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.49 (br.s, 3H), 7.37 (br.t, 1H), 7.41-7.62 (m, 7H), 7.69 (br.t, 1H), 8.08 (br.d, 1H), 8.87 (d, 1H); HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.56 min.
Example 242
Methyl-phenyl-carbamic acid 5-methyl~isoxazoI-3-yl ester
A mixture of 3-hydroxy-5-methylisoxazole (0.30 g, 3.00 mmol)), 1-methyl-3-(methyI-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02) ethyl acetaterheptane (25:75)) yielding the title compound (0.67 g, 96% yield) as a colourless oil.
1H NMR (300 MHz, CDCI3): £2.40 (s, 3H), 3.40 (br.s, 3H), 6.14 (br.s, 1H), 7.28-7.44 (m, 5H); HPLC-MS (Method A): mlz = 255 (M+Na); Rt = 3.31 min.
Example 243
Methyl-phenyl-rarbamic acid quinoxalin-2-yl ester
A mixture of 2-hydroxyquinoxaline (0.44 g, 3.00 mmol)), 1-methyl-3-(methyI-phenyl-carbamoyI)-3H-imidazoM-ium iodide (1.03 g, 3.00. mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 40 °C for 24 hours. The solvent was evaporated in vacuo and the residue was purified

by flash column chromatography (Si02, ethyl acetate:heptane (30:70)) yielding the title compound (0.65 g, 77% yield) as a white solid..
1H NMR (300 MHz, CDCl3): £3.48 (br.s, 3H), 7.29 (m, 1H), 7.41 (mf 4H), 7.72 (m, 2H), 8.00 (m, 1H), 8.10 (m, 1H), 8.67 (br.s, 1H); HPLC-MS (Method A): mlz = 280 (M+H); Rt = 3.66 min.
Example 244
Methyl-phenyl-carbamic acid 4-methyI-quinolin-2-yI ester
A mixture of 2-hydroxy-4-methylquinoIine (0.48 g, 3.00 mmol) )f 1-methyI-3-(methyl-phenyI-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 50 °C for 4 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70)) yielding the title compound (0.24 g, 27% yield) as a white solid.
1H NMR (300 MHz, CDCI3): £2.70 (s, 3H), 3.49 (br.s, 3H), 7.08 (m, 1H), 7.27 (mf 1H), 7.40 (m, 4H), 7.53 (tf 1H), 7.69 (t, 1H), 7.96 (d, 1H), 8.00 (d, 1H); HPLC-MS (Method A): mfz = 293 (M+H); Rt = 3.88 min.
Example 245
Methyl-phenyl-carbamic acid 3-methyl-quindxaIin-2-yl ester
A mbcture of 2-hydroxy-3-methylquinoxaline (0.48 g, 3.00 mmol)), 1-methyl-3-(methyl-pheny!-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02r ethyl acetate:heptane (50:50)) yielding the title compound (0.59 g, 67% yield) as a white solid.
1H NMR (300 MHz, CDCI3): £2.61 (br.s, 3H), 3.48 (br.s, 3H), 7.30 (m, 1H), 7.42 (m, 4H), 7.69 (m, 2H), 7.99 (m, 2H); HPLC-MS (Method A): mlz = 294 (M+H); Rt = 3.92 min.
Example 246
Methyl-phenyl-carbamic acid 4,6-dimethyl-pyrimidin-2-yl ester
A solution of 4,6-dimethyl-2-hydroxypyrimidine (0.37 g, 3.00 mmol)), 1-methyl-3-(methyl-

phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmo!) and triethylamine (0,42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.46 g, 60% yield) as a white solid.
1H NMR (300 MHz, CDCl3): 52.48 (s, 6H), 3.43 (br.s, 3H), 6.92 (br.s, 1H), 7.22 (m, 1H), 7.37 (m, 4H); HPLC-MS (Method A): miz = 258 (M+H); Rt = 2.77 min.
Example 247
Methyl-phenyl-carbarnic acid isoquinolin-6-yl ester
A solution of 6-hydroxyquinoIine (0.44 g, 3.00 mmol), 1-methyl-3-(methyl-phenyI-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmo!) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02l ethyl ace-tate:heptane (50:50)) yielding the title compound (0.80 g, 96% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.47 (s, 3H), 7.28 (mf 1H), 7.33-7.54 (m, 6H), 7.59 (s, 1H), 8.08 (d, 2H), 8.86 (m, 1H); HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.63 min.
Example 248
Methyl-phenyl-carbarnic acid quinolin-2-yl ester
A solution of 2-hydroxyquinoline (0.44 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. More acetonitriie (60 ml) was. added and the solution was heated at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (40:60)) yielding the title compound (0.33 g, 40% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.50 (br.s, 3H), 7.14-7.30 (m, 2H), 7.42 (m, 4H), 7.52 (t, 1H), 7.71 (t, 1H), 7.82 (d, 1H), 8.00 (dt 1H), 8.19 (d, 1H); HPLC-MS (Method A): m/z= 279 (M+H); Rt=3.91 min.
Example 249
Methyl-phenyl-carbarnic acid isoquinolin-3-yl ester

A solution of 3-hydroxyisoquinoline (0.44 g, 3.00 mmol), 1-methyi-3-(methyl-phenyI-carbamoy!)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.82 g, 99% yield) as a white solid.
1H NMR (300MHz, CDCl3): £3.49 (br,s, 3H)F 7.24 (mf 1H), 7.33-7.47 (m, 5H), 7.51 (t, 1H), 7.63 (t, 1H), 7.77 (d, 1H),7.94 (d, 1H), 9.06 (s, 1H); HPLC-MS (Method A): m/z= 279 (M+H); Rt = 3.68 min.
Example 250
Methyl-phenyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yI ester
A solution of 4-(trifIuoromethyI)-2-pyrimidol (0,49 g, 3.00 mmol), 1-methyI-3-(methyl-phenyI-carbamoyI)-3H-imidazol-1-iurn iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate-.heptane (30:70)) yielding the title compound (0.35 g, 39% yield) as a colourless oil.
1H NMR (300MHz, CDCI3): £3.45 (br.s, 3H), 7.28 (m, 1H), 7.38 (m, 4H), 7.52 (br.s, 1H), 8.93 (br.s, 1H); HPLC-MS (Method A): m/z= 320 (M+Na); Rt= 3.58 min.
Example 251
Morpholine-4-carboxyIic acid 4-trifIuoromethyl-pyrimidin-2-yl ester
A solution of 4-(trifluorc>methyI)-2-pyrimidoi (0.49 g, 3.00 mmol), 4-morpholinecarbonyl chloride (0.45 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.51 g, 3.00 mmol) in N,N-dimethylformamide (15 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70 -» 50:50)) yielding the title compound (0.66 g, 80% yield) as a white solid.
1H NMR (300MHz, CDCl3): £3.57-3.81 (m, 8H), 7.57 (d, 1H), 8.97 (d, 1H).; HPLC-MS (Method A): mfz^ 300. (M+Na); Rt = 2.36 min.

Example 252
Methyl-phenyl-carbamic acid 3-nitn>pyridin-2-yI ester
A solution of 2-hydroxy-3-nitropyridine (0.42 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-caitamoyf)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 m!) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate;heptane (40:60)) yielding the title compound (0.41 g, 50% yield) as a yellow solid.
1H NMR (300MHz, CDCI3): £3.41 + 3.58 (2 x br.s, 3H), 7.30 (m, 1H), 7.42 (m, 5H), 8.45 (br.d, 1H), 8.49 (br.s, 1H); HPLC-MS (Method A): mlz = 296 (M+Na); Rt = 3.22 min.
Example 253
Methyl-phenyl-carbamic acid 5-chloro-pyridin-2-yI ester
A solution of 5-chloro-2-pyridol (0.39 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl ace-tate:heptane (30:70)) yielding the title compound (0.78 g, 99% yield) as a white solid. 1H NMR (300MHz, CDCl3): 53.44 (br.s, 3H), 7.00 (br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.69 (d, 1H), 8.30 (d, 1H); HPLC-MS (Method A): mlz = 285 (M+Na); Rt = 3.47 min.
Example 254
Methyl-phenyl-carbamic acid 5-(2-nitro-phenyl)-pyrimidin-2-yl ester
A solution of 5-(2-nitrophenyl)-pyrimidin-2-ol (0.35 g, 1.61 mmol), 1-methyl-3-(methyl-phenyl-carbamoyI)-3tf-imidazol-1-ium iodide (0.55 g, 1.61 mmol). and triethylamine (0.22 ml, 1.61 mmol) in acetonitrile (15 ml) was heated at 50 °C for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl ace-tateiheptane (50:50)) yielding the title compound (0.18 g, 32% yield) as a yellow oil. 1H NMR (300MHz, CDCI3): £3.47 (br.s, 3H), 7.29 (m, 1H), 7.40 (m, 5H), 7.63 (dt, 1H), 7.72 (dt, 1H), 8.10 (d, 1H), 8.61 (br.s, 2H); HPLC-MS (Method A): mlz = 351 (M+H), 373 (M+Na), 723 (2M+Na).; Rt = 3.65 min.

Example 255
Methyl-phenyi-carbamic acid 5-trifluoromethyI-pyridin-2-yl ester
A solution of 2-hydroxy-5-(trifluoromethyI)pyridine (0.49 g, 3.00 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02) ethyl acetate:heptane (15:85)) yielding the title compound (0.59 g, 66% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 7.23 (br.s, 1H), 7.28 (m, 1H)r 7.37 (m, 4H), 7.94 (br.d, 1H), 8.62 (br.s, 1H); HPLC-MS (Method A): m/z= 319 (M+Na); Rt = 3.85 min.
Example 256
Methyl-phenyi-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yI ester
A solution of 3-chloro-5-(trifluoromethyI)"2-pyridinol (0.59 g, 3.00 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (15:85)) yielding the title compound (146 mg, 15% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 7.30 (m, 1H), 7.40 (d, 4H), 8.00 (br.s, 1H), 8.52 (br.s, 1H).; HPLC-MS (Method A): mfz = 353 (M+Na); Rt = 4.29. min.
Example 257
Methyl-phenyi-carbamic acid 5-nitro-3-trifluoromethyl-pyridin-2-yl ester
A solution of 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (0,36 g, 1.73 mmol), N-methyl-N-phenylcarbamoyl chloride (0.44 g, 2.59 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.29 g, 2.59 mmol) in tetrahydrofuran (15 ml), was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the. residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (15:85)) yielding the title compound (0.55 g, 92% yield) as an orange solid..
1H NMR (300MHz, CDCI3): (53.46 (br.s, 3H), 7.23-7.46 (m, 5H), 8.70 (br.s, 1H), 9.37 (br.s, 1H); HPLC-MS (Method A): mlz = 364 (M+H); Rt = 4.08 min.

Example 258
(3-Chloro-phenyI)-methyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester
At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyI-2-hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was removed and stirring was continued at room temperature for 1 hour. (3-ChIorophenyI)-methylamine (0,35 g, 2.50 mmot) was added to one-fourth of the solution. After stirring overnight at room temperature the solvent was evaporated In vacuo and the residue was purified by flash column chromatography (Si02( ethyl acetate:heptane (20:80)) followed by preparative HPLC, yielding the title compound (332 mg, 40%) as a colourless oil. 1H NMR (300MHz, CDCI3): S3.45 (br.s, 3H), 7.23-7.44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H); HPLC-MS (Method A): m/z= 354 (M+H); Rt = 4.03 min.
Example 259
Methyl-m-tolyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester
At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyI-2-hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was removed and stirring was continued at room temperature for 1 hour. Methykn-tolyl-amine (0,30 g, 2.50 mmol) was added to one-fourth of the solution. After stirring overnight at room temperature the solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (20:80)) followed by preparative HPLC, yielding the title compound (51 mg, 7%) as a colourless oil.
1H NMR (300MHz, CDCi3): 52.37 (s, 3H). 3.42 (br.s, 3H), 7.07-7.31 (m, 4H)f 7.52 (br.s, 1H), 8.92 (br.s, 1H); HPLC-MS (Method A): mlz = 334 (M+Na); Rt = 3.92 min.
Example 260
Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester
A solution of 4-trifluoromethyl-2-hydroxypyrimidine (0.49 g, 3.00 mmol), 4-morpholinecarbonyl chloride (0.45 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water and brine were added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The

residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70 -* 50:50)) yielding the title compound (0.66 g, 80% yield) as. a white solid. 'H NMR (300MHz, CDCI3): 53.45 (br.s, 3H), 7.23-7.44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H); HPLC-MS (Method A): mlz = 354 (M+H); Rt =. 4.03 min.
Example 261
Methyl-phenyl-carbamic acid 4,5-dichloro-pyridazin-3-yl ester
A solution of 4,5-dichloro-3-hydroxypyridazine (0.49 g, 3.00 mmol), Af-methyl-W-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in tet-rahydrofuran (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02j ethyl acetate:heptane (20:80)) yielding the title compound (0.12 g, 14% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.50 (s, 3H), 7.18-7.32 (m. 5H), 7.63 (s, 1H); HPLC-MS (Method A): mlz = 320 (M+Na); Rt = 2.91 min.
Example 262
Methyl-phenyl-carbamic acid 5-benzoylamino-pyridin-2-yI ester
A solution of N-(6-hydroxy-pyridin-3-yl)-benzamide (0.64 g, 3.00 mmol), A/-methyl-/V-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in di-chloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in ethyl acetate and filtered over a short pad of silica. Evaporation of the solvent in vacuo yielded the title compound (0.70 g, 68% yield) as a thick oil.
1H NMR (300MHz, CDCI3): £3.40 (br.s, 3H), 6.90 (br.s, 1H), 7.26 (m, 1H), 7.31-7.44 (m, 6H), 7.50 (m, 1H), 7.88 (d, 2H), 8.08 (dd, 1H)( 8.37 (d, 1H)f 8.79 (br.s, 1H); HPLC-MS (Method A): mlz = 348 (M+H); Rt = 3.49 min.
Example 263
Methyl-phenyl-carbamic acid 5-(cyclohexanecarbonyI-amino)-pyridin-2-yl ester
A solution of cyclohexanecarboxylic acid (6-hydroxy-pyridin-3-yI)-amide (0.66 g, 3.00 mmol),

N-methyl-A/-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1,4-diazabicycio[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.75 g, 71% yield) as a slightly coloured solid.
1H NMR (300MHz, CDCI3): 51.18-1.33 (m, 3H), 1.42-1.59 (m, 2H), 1.60 (m, 1H), 1.77-1.94 (m, 4H), 2.20 (m, 1H), 3.45 (br.s, 3H), 6.91 (br.s, 1H), 7.28 (m, 1H), 7.39 (m, 4H), 7.94 (br.s, 1H)( 8.00 (dd, 1H), 8.20 (d, 1H); HPLC-MS (Method A): mlz = 354 (M+H); Rt = 3.74 rnin.
Example 264
Methyl-phenyl-carbamic acid 4,4-dimethyI-2,6-dioxo-3,4,5)6-tetrahydro-2H-[1 ^bipyridinyl-e1-yl ester
A solution of e'-hydroxy-4,4-dimethyl-4,5-dihydro-SH-tl^lbipyridinyl-^e-dione (0.70 g, 3.00 mmol), /V-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmo!) and 1,4-diazabi-cyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction and subsequently dried in a vacuum oven yielding the title compound (0,75 g, 71% yield) as a white solid.
1H NMR (300MHz, CDCI3): 1.20 (s, 6H), 2.68 (s, 4H), 3.44. (br.s, 3H), 7.14 (br.s, 1H), 7.25 (m, 1H), 7.37 (m, 4H), 7.48 (br.d, 1H), 8.08 (d, 1H); HPLC-MS (Method A): m/z= 368 (M+H); Rt = 3.41 min.
Example 265
Methyl-phenyl-carbamic acid 5-(2f2-dimethyKpropionyIamino)-pyridin-2-yl ester
A solution of A/^e-hydroxy-pyridin-S-yl^^-dimethyl-propionamide (0.58 g, 3.00 mmol), /V-methyl-A/-phenylcarbamoyI chloride (0.51 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 1 hour. Water was added and a thick oil was being formed. The water was decanted and the residue was dissolved in dichloromethane. The solution was dried over sodium sulphate, filtered and evaporated in vacuo yielding the title compound (0.55 g, 56% yield) as a brown oil that solidified upon standing. 1H NMR (300MHz, CDCI3): S1.29 (s, 9H), 3.43 (br.s, 3H)f 6.97 (br.s, 1H), 7.26 (m, 1H), 7.38

(m, 4H), 7.64 (br.s, 1H), 8.10 (dd, 1H)f 8.28 (br.s, 1H); HPLC-MS (Method A): m/z= 348 (M+H); Rt = 3.49 min.
Example 266
Methyl-phenyl-carbamic acid 5-(2-cydohexyl-acetylamino)-pyridin-2-yl ester
A solution, of 2-cyclohexyl-N-(6-hydroxy-pyridin-3-yI)-acetamide (0.70 g, 3.00 mmol), N-methyl-W-phenylcarbamoyl chloride (0.51 g, 3.00 mmo!) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmo!) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.79 g, 72% yield) as a brown solid.
1H NMR (300MHz, CDCI3): $0.86-1.01 (m, 2H), 1.05-1.37 (m, 3H), 1.60-1.78 (m, 5H), 1.83 (m, 1H). 2.13 (d, 2H), 3.46 (br.s, 3H), 6.90 (br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.98 (d, 1H), 8.12 (s + br.s, 2H, CH + NH); HPLC-MS (Method A): m/z= 368 (M+H); Rt = 4.04 min.
Example 267
Methyl-phenyl-carbamic acid 5-(4-methoxy-phenoxy)-pyrimidin-2-yI ester
A solution of 5-(4-methoxy-phenoxy)-pyrimidin-2-ol (0.44 g( 2.00 mmol), A/-methyl-/V-phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 -hour. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetaterheptane yielding the title compound (0.55 g, 79% yield) as an off-white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 3.82 (s, 3H), 6.91 + 7.00 (AB-system, 2 x 2H), 7.26 (m, 1H), 6.39 (m, 4H), 8.33 (s, 2H); HPLC-MS (Method A): m/z = 352 (M+H); Rt = 4.02 min.
Example 268
Methyl-phenyl-carbamic acid 5-(3,4-dichloro-phenoxy)-pyrimidin-2-yl ester
A solution of 5-(3,4-dichloro-phenoxy)-pyrimidin-2-oI (0.51 g, 2.00 mmol), A/-methyl-/V-

phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1,4-diazabicycld[2.2.2]octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates, were collected by. suction. The solids were dissolved in di-chioromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.51 g, 65% yield) as an off-white solid.,
1H NMR (300MHz, CDCI3): £3.44 (br.s, 3H), 6.89 (dd, 1H), 7.14 (d, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.44 (d, 1H), 8.42 (s, 2H); HPLC-MS (Method A): mlz = 390 (M+H); Rt = 4.66 min.
Example 269
Methyl-phenyl-carbamic acid 6-pyridin-2-ylmethyl-pyridazin-3-yl ester
A solution of 6-(2-pyridinylmethy!)-3-pyridazinol (100 mg, 0.53 mmol), N-methyl-N-phenylcarbamoyl chloride (91 mg, 0.53 mmol) and 1,4-diazabicyclo[2.2.2]octane (60 mg, 0.53 mmol) in dimethylformamide (10 m!) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02) ethyl acetate) yielding the title compound (70 mgt 41% yield) as a yellow oil.
1H NMR (300MHz, CDCI3): 53.42 (br.s, 3H), 4.50 (s, 2H), 7.11-7.33 (m. 4H), 7.39 (d, 4H), 7.60 (m, 2H), 8.52 (d, 1H); HPLC-MS (Method A): mlz = 321 (M+H); Rt = 1.98 min.
Example 270
Methyl-phenyl-carbamic acid 6-(4-methoxy-benzyI)-pyridazin-3-yl ester
A solution of 6-(2-pyridinylmethyl)-3-pyridazinol (97 mg, 0.45 mmol), /V-methyl-N-phenylcarbamoyl chloride (76 mg, 0.45 mmol) and 1,4-diazabicydo[2.2.2]octane (50 mg, 0.45 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (117 mg, 41 % yield) as a white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 3.79 (s, 3H), 4.28 (s, 2H), 6.83 (d, 2H), 7.17 (d, 2H), 7.27 (m, 3H), 7.40 (d, 4H); HPLC-MS (Method A): mlz = 350 (M+H); Rt = 3.60 min.

Example 271
Methyl-phenyl-carbamic acid 6-(2,4-dichIoro-benzyl)-pyriclazin-3-yl ester
A solution of 6-(2,4-dichlorobenzyI)-3-pyridazinol (98 mg, 0.38 mmol), A/-methyI-N-phenylcarbamoyl chloride (65 mg, 0.38 mmol) and 1,44iazabicydo[2.2.2]otiane (43 mg, 0.38 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water
was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetaterheptane (40:60)) yielding the title compound (119 mg, 80% yield) as a yellow oil.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 4.42 (s, 2H), 7.17-7.44 (m, 10H); HPLC-MS (Method A): miz = 388 (M+H); R, = 4.44 min.
Example 272 (General procedure 15)
4-Pyridin-2-yl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)phenyl chloroformate and 1-pyridin-2-yI-piperazine. White crystals, yield 87 %; m.p. 247 - 248 °C; HPLC-MS: m/z = 445 (M+H); IR (KBr): v 1713 (C=0) cm"1.
Example 273 (General procedure 15)
4-(1,3-Benzodioxol-5-yI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2~yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(1,3-benzodioxol-5-yI)-piperazine. The crude product was partitioned between dichlorormethane and 1 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound. Yield 39 %; m.p. 146 -147 °C; 1H NMR (DMSO-cf6): £8.60 - 8.56 (br, 1H), 8.29 -8.20 (dd-like, 1H), 7.31 - 7.20 (m, 5H), 6.84 - 6.72 (d-like, 1H), 6.76 - 6.72 (d-iike, 1H), 6.45 -6.36 (dd-Iike, 1H), 3.81 - 3.47 (br m, 4H), 3.16.-3.00 (br,m, 4H); HPLC-MS: m/z = 488 (M+H); IR (KBr): v 1719 (C=0) cm"1.
Example 274 (General procedure 15)

4-[2-(2-Hydroxyethoxy)ethyI]-piperazine-1 -carboxylic acid 4-(5-trifluorometnyi-pynain-^-yloxy)-phenyl ester
The hydrochloride, of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 2-(2-hydroxyethoxy)ethyl-piperazine. Yield 13 %; 1H NMR (DMSO-cfc): £ 10.8 (br), 8.61 - 8.54 (br, 1H)f 8.30 - 8.21 (dd-Iike, 1H), 7.32 - 7.19 (m, 5H), 4.3 - 3.9 (br, 2H), 3.9 - 3.0 (br m, alicyclics and aiiphatics + water); HPLC-MS: m/z = 456(M+H); !R(KBr):v1724(C=0)cm'1.
Example 275 (General procedure 15)
4-(DiphenyImethyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl chloroformate and 1-(diphenylmethy!)piperazine, white crystals, yield 74 %; m.p. 168- 169 °C;
1H NMR (DMSO-d6); S 12.4 (br, 1H), 8.60 - 8.54 (d-Iike m, 1H), 8.28 - 8.20 (dd-like rn, 1H), 7.98 - 7.82 (br, 2H), 7.55 - 7.15 (br m, 13 H), 5.6 (br, 1H), 4.35 - 3.48 (br, 3H), 3.35 - 3.0 (br, 5H); IR (KBr): v 1723 (C=0) cm"1.
Example 276 (General procedure 15)
4-(4~tert-ButylbenzyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifIuoromethyI~pyridin-2-yloxy)-phenyl chloroformate and 1-(4-ferf-butyIbenzyl)diphenylmethyl)piperazineJ white crystals, yield 56 %; m.p. 274 - 275 °C; HPLOMS: m/z = 514 (M+H); IR (KBr): v 1721 (C=0) cm-Example 277 (General procedure 15)
4-(4-Fluorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-fluorobenzyl)piperazinel white crystals, yield 69 %;

m.p. 240 - 243 °C; HPLC-MS: mfe = 476 (M+H), 498 (M+Na); IR (KBr): v 1720 (C=0) cm"1.
Example 278 (General procedure 15)
4-(2-ThienylethyI)pipera2ine-1-cart>oxylic acid 4-(54rifluoromethyl-pyridin-2-yioxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-thienyIethy[)piperazine, white crystals, yield 62 %; m.p. 236 - 237 °C; 1H NMR (DMSO-cf6): 511.51 (br s, 1H), 8.61 - 8.54 (br m, 1H), 7.48 -7.17 (m, 6H), 7.06 - 6.89 (m, 2H), 4.4 - 3.9 (br, 2H), 3.9 - 2.6 (br m, 15.5 H ~ 12H + water); HPLC-MS: m/z = 478 (M+H); IR (KBr): v 1714 (C=0) cm-1.
Example 279 (General procedure 15)
4-(1-PhenyIethyI)piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester
The crude hydrochloride of the title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yIoxy)-phenyl chloroformate and l~(1-phenylethyl)piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m.p. 242 °C; 1H NMR (DMSO-ofe): S11.56 (br s, 1H), 8.61 - 8.52 (br m, 1H), 8.30. - 8.19 (dd-like m, 1H), 7.77 - 7.31 (br. m, 5H), 7.31 - 7.13 (m, 5H), 4.60 - 3.27 (br m, 6H + water), 3.27 - 2.57 (br, 3H), 1.73 (br d, 3H); IR (KBr): v 1712 (C=0) cm"1.
Example 280 (General procedure 15)
4-Octylpiperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester
The crude hydrochloride of the title compound was prepared from4-(5-trifluoromethyl-pyiidin-2-yloxy)-phenyl chloroformate and 1-(1-phenylethyl)piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m.p. 244-245 °C; 1H NMR (DMSO-cfe): 511-16 (br s, 1H), 8.61 - 8.57 (br m, 1H), 8.30 - 8.20 (dd-like mT 1H)f 7.32 - 7.18 (m, 5H), 4.39 - 3.96 (br, 2H), 3,77 - 3.38 (br, 4H), 3.25 - 2.88 (br, 4H), 1.84 -1.58 (br, 2H), 1.42 - 1.12 (br s, 10H), 0.87 (br t, 3H); IR (KBr): v 1731,1713 (C=0) cm"1.
Example 281 (General procedure 15)
4-(3-Dimethylamino-propyl)-piperazine-1 -carboxylic acid 4«(5"trifluoromethyl-pyridin-2-yloxy)-

phenyl ester
The crude hydrochloride of the title compound was prepared from 4-(5-trifluorornethyl-pyridin-2-yloxy)-phenyI chloroformate and 1-(3-dimethylaminopropyl)piperazine. A suspension of the product in ether was stirred with an excess of HCI in ether and the precipitate was washed with ether and dried to give the dihydrochloride of the title compound as white crystals, m.p. 292 - 293 °C; 'H NMR (DMSO-cf6): S11.35 (br s, 1H), 10.46. (br s, 1H), 8.61 - 8.52 (br m, 1H), 8.31 - 8.17 (m, 1H), 7.35 - 7.16 (m, 5H), 4.45 - 4.00 (br, 2H), 3.80 - 3.45 (br, 4H), 3.30 - 3.01 (br, 6H), 2.78 (br s, 6H), 2.31 - 2.07 (br, 2H); lR (KBr): v 1731, 1713 (C=0) cm-1.
Example 282 (General procedure 15)
4-Pyrimidin-2-yI-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yioxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifiuoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(pyrimidin-2-yI)piperazine. The crude product was dried in vacuo at 50 °C for 80 min and extracted with ether. The ether phase was evaporated and the residue was purified by flash chromatography on silica eluted with ethyl acetate - heptane 1:1 to give the title compound as white needles. Yield 14 %; m.p. 120-121 °C; 1H NMR (DMSO-af6): £8.61 - 8.56 (br, 1H), 8.41 (d, J = 4.8 Hz, 2H)f 8.29 - 8.20 (dd-like, 1H), 7.31 - 7.20 (m, 5H), 6,69 (Hike m, J - 4.8 Hz, 1H), 3.94 - 3.78 (br s, 4H), 3.78 - 3.45 (br d, 4H); HPLC-MS: m/z = 446 (M+H); lR (KBr): v 1719 (C=0) cm"1.
Example 283 (General procedure 15)
4-CycIopropylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-cyclopropyIpiperazine, yield 62 %. Recrystallisation from 0.2 M HCI gave white, crystals, m.p. 238 - 239 °C; 1H NMR (DMSO-cfe): 611.51 (br s, 1H), 8.61 - 8.55 (m, 1H), 8.30 - 8.20 ( m, dd, 1H), 7.32 - 7.19 (m, d+s, 5H), 4.44 - 4.00 (br, 2H), 3.80 - 3.40 (br m, 4H), 3.29 - 2.93 (br m, 4H), 1.28 - 1.05 (br m, 1H), 0.75 - 0.58 (m, 2H), 0.50 - 0.35 (m, 2H).IR (KBr): v 1730, 1713 (C=0) cm"1.
Example 284 (General procedure 15)
4-Methyl-1,4-diazepane-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester

The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-methylhomopiperazine; white crystals, m.p. 210 - 211 °C; 1H NMR (DMSO-d6): 511.27 (br s, 1H), 8.61 - 8,54 (m, 1H), 8.30 - 8.20 (dd-Iike m, 1H). 7.34 - 7.18 (m, 5H), 4.13 - 3.08 (br, 11H, 8H + water), 2.80 (br s, 3H), 2.47 -1.98 (br m, 2H); IR (KBr): v 1723, 1711 (C=0) cm"1.
Example 285. (General procedure 15)
4-Phenethyl-piperazine-1-carboxylic acid 4-(5-trifluorornethyI-pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-y!oxy)-phenyI chloroformate and 1-phenethylpiperazine, yield 54 %. Recrystallisation from 99% EtOH gave white crystals, m.p. 245 - 247 °C; 1H NMR (DMSOcf6): 8 11.72 (br, 1H), 8.63 - 8.53 (br, 1H), 8.31 - 8.19 (dd-Iike m, 1H), 7.44 - 7.16 (m, 10H), 4.44 - 4.01 (br, 2H), 3.83.-3.45 (br, 4H), 3.45 - 2.95 (br, ~8H, 6H + water); IR (KBr): v 1713 (C=0) cm-1.
Example 286 (General procedure 15)
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifiuoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-pyridin-2-yImethyl-piperazine. White crystals, yield 64 %; m.p. 189 - 190 °C; 1H NMR (DMSO-d6): 58.72 - 8.63 (m, 1H), 8.60 - 8.55 (br, 1H), 8.29 -8.20 (dd-Iike, 1H), 8.02 - 7.90 (m( 1H). 7.80 - 7.65 (m, 1H)r 7.56 - 7.45 (m. 1H)f 7.31- 7.22 (m, 5H), 4.52 (br. s, 2H), 4.06 - 3.68 (br s, 4H), 3.68 - 2.93 (br, 4H + NH + water); HPLC-MS: m/z = 459 (M+H); IR (KBr): v 1717 (C=0) cm"1.
Example 287 (General procedure 15)
4-Pyridin-3-y)methyl-piperazine-1 -carboxylic acid 4-(5-trif luoromethyl-pyridin-2-yloxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine. Trituration with water, filtering and drying of the residue gave white crystals. 1H NMR (DMSO-cfe): £8.78 - 8.51 (m, 3H), 8.30 - 8.18 (dd-Iike, 1H), 8.12 - 8.00 (br d, 1H), 7.57 -7.46 (m, 1H), 7.32 - 7.17 (m, 5H), 4.65

- 4.11 (br, 2H), 4.11 - 2.78 (br m, 6H + water); HPLC-MS: m/z = 459 (M+H); IR (KBr): v 1723
(00) cm"1.
Example 288 (General procedure 15)
4-(3-Phenylpropyl)piperazine-1 -carboxylic acid 4-(54rifluoromethyl-pyridin«2-yloxy)-phenyI
ester
The hydrochloride, of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(3-phenylpropyl)piperazine, yield 68 %. m.p. 235 - 238 °C; 1H NMR(DMSO-d6): 5 11.51 (br, 1H), 8.61 -8.55.(br, 1H), 8.29 - 8.20 (dd-like m, 1H)f 7.38 - 7.16 (m, 10H), 4.38 - 3.96 (br, 2H), 3.83 - 3.40 (br, 4H), 3.30 - 2.91 (br, 4H), 2.75 - 2.57 (Hike m, 2H), 2.20 -1.94 (m, 2H); IR (KBr): v 1715 (C=0) cm"1.
Example 289 (General procedure 15)
4-(4-PhenylbutyI)piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-phenyIbutyI)piperazine, yield 71 %. m.p. 232 - 234 °C;
1H NMR (DMSO-cf6): tf 11.32 (br s, 1H), 8.61 - 8.55 (br, 1H), 8.29- 8.20. (dd-like m, 1H), 7.36
- 7.13 (m, 10H), 4.4Q - 3-97 (br, 2H), 3.81 - 3.39 (br m, 4H), 3.26 - 2.91 (br, 4H), 2.71 - 2.55
(t-like m, 2H)f 1.88 -1.51 (br m, 4H); IR (KBr): v 1728,1713 (C=0) cm"1.
Example 290 (General procedure 15)
4-Benzyl-1,4-diazepane-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title, compound was prepared from 4-(5-trifluoromethyl«pyridin-2-yloxy)-phenyl chloroformate and 1-benzyIhomopiperazine, crude yield 70 %. 0.20 g Of the crude product was heated with 3 ml of water, cooled at 0 °C, the precipitate filtered off and dried; m.p. 231 - 233 °C; 1H NMR (DMSO-of6): 811.38 (br s, 1H), 8.62 - 8.55 (br, 1 H)r 8.30 -8.20 (dd-like m, 1H), 7.76 - 7.60 (br, 2H), 7.52- 7.41 (br m, 3H), 7.32 - 7.19 (m. 5H), 4.38 (br s, 2H), 4.18 - 3.01 (br m, 8H + water), 2.6 - Z0 (brf 2H + DMSO); IR (KBr): v 1726,1710 (C=0) cm"1.

Example 291 (General procedure 15)
4-(3,4-DichlorophenyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl chloroformate and 1-(3,4-dichlorophenyl)piperazine. The crude product was partitioned between dichlorormethane and 2 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound as white crystals. Yield 28 %; m.p. 115 -116 °C; 1H NMR (DMSO-cf6): 8 8.61 -8.55 (br, 1H), 8.30 - 8.20 (dd-like, 1H), 7.48 - 7.40 (d-Iike,1H), 7.31 - 7.16 (m, 6H), 7.04 - 6.94 (dd-like, 1H), 3.83 - 3.47 (br m, 4H), 3.36 - 3.24 (br s, 4H + water); HPLC-MS: m/z = 512 (M+H); IR (KBr): v 1724,1706 cm"1.
Example 292 (General procedure 15)
4-(4-Fluorophenyt)piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5~trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-fluoropheny()piperazine. White crystals, yield 20 %; m.p. 131-132 °C; 1H NMR (DMSO-cf6): 8 8.61 - 8.53 (br, 1H), 8.30 - 8.19 (dd-like, 1H), 7.33 -7.17 (m, 5H), 7.17 - 6.95 (m, 4H), 3.85 - 3.47 (br d, 4H), 3.25 - 3.07 (br m, 4H); HPLC-MS: m/z = 462 (M+H); IR (KBr): v 1739,1714 cm'1.
Example 293 (General procedure 15)
4-(2-ChlorophenyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl
ester
The the hydrochloride of title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-chlorophenyl)piperazine. Drying in vacuo at 50 °C for 3Yz h gave the title compound; 1H NMR (DMSO-of6): £8.61 - 8.55 (br, 1H), 8.29 - 8.20 (dd-like, 1H), 7.53-7.41 (m, 1H), 7.39 - 7.17 (m, 7H), 7.14 - 7.03 (m, 1H), 4.58 (br s, NH + water), 3.85 - 3.55 (br m, 4H), 3.12 - 2.99 (br m, 4H); HPLOMS: m/z = 478 (M+H); IR (KBr): v 1733(C=0)cm-
Example 294 (General procedure 15)
(2-Dimethylamino-ethyl)methyicarbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and N,N,N'-trimethyIethylenediamine; m.p. 139 -140 °C; 1H NMR (MeOH-de): 8 8.45 - 8.38 (br, 1H), 8.15 - 8.05 (dd-!ike m, 1H), 7.31 - 7.11 (m, 5H), 3.84 - 3.73 (br m, 2H), 3.54 - 3.38 (br m, 3H), 3.19 (br s, 2H)f 2.99 (br s, 6H); traces of impurities at 3.9 (br) and 3.1 (br); lR (KBr): v 2695, 1705 cm 1 (C=0) cm"1.
Example 295 (General procedure 15) 4-Methylpiperazine-1~carboxyIic acid 4-chIorophenyl ester
The hydrochloride of the title compound was prepared from 4-chlorophenyI chloroformate and 1-methy!piperazinef yield 81 %. White crystals, m.p. 237 - 240 DC; 1H NMR (DMSO-of6): 11.67 (br s, 1H), 7.50, 7.45, 7.24, 7.20 (AB-system, d = 7.47 and 7.22; J = 8.84 Hz, 4H), 4.40 - 3.91 (br, 2H, 3.77 - 2.92 (br m, 6H + water), 2.77 (s, 3H); IR (KBr): v 1717 (C=0) cm"1.
Example 296 (General procedure 15) 4-(4-PhenylbutyI)piperazine-1-carboxylic acid 4-chlorophenyl ester
The hydrochloride of the title compound was prepared from 4-chlorophenyl chloroformate and 1-(4-phenylbutyl)piperazine, yield 86 %. White crystals, m.p. 230 - 232 °C; 1H NMR (DMSO-cfe): 8 11.43 (br, 1H), 7.51 - 7.43 (d-like m, 2H), 7.33 - 7.15 (m, 7H), 4.33 - 3.95 (br, max at 4.21 and 4,10 ppm; 2H), 3.72 - 3.36 (br m, 4H), 3.22 - 2.96 (br, max at 3.10 ppm, 4H)f 2.62 (t, J= 7.54 Hz, 2H), 1.84 - 1.69 (m, 2H), 1.69 -1.54 (m, 2H) ppm; IR (KBr): v 1736,1720 (C=0) cm'1.
Example 297 (General procedure 15)
4-[2-(2-Hydroxyethoxy)ethyI]piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 2-(2-hydroxyethoxy)ethyI-piperazine. Pale powder, m.p. 176 -178 °C; 1H NMR (MeOH-d4): 5 Two AB-systems: 7.68 - 7.58 (d-like, 2H)

and 7.29 - 7.04 (m, 6H); 4.74 - 3.18 (complex, 16 H, partly overlapping with MeOH-tf4); HPLC-MS m/z = 455 (M+H), 477 (M+Na), Rt= 3.08 min.; IR (KBr): v 1718 (C=0) cm"1.
Example 298 (General procedure 15)
4-(1-EthylpropyI)piperazine-1-carboxyIic acid 4-(4-trifluoromethylphenoxy)phenyl ester
The hydrochloride of the title compound was. prepared from 4-(4-trifluoromethylphenoxy)phenyl chloroformate and 1-(1-ethylpropyI)piperazine, yield 74 %. White crystals, 1H NMR (DMSO-d6): 510.59 (brs, 1H), 2 AB-systems: 7.81 -7.70 (d-like, 2H) and 7.31 - 7.09 (m, 6H); 4.38 -3.99 (br s, 2H), 3.90 - 3.38 (br, 4H), 3.33- 2.99 (br, 3H), 2.01 - 1.77 (m, 2H), 1.77 -1.49 (m, 2H), 0.98 (t, 6H); HPLC-MS m/z = 437 (M+H).
Example 299 (General procedure 15)
4-CycIoheptyipiperazine-1-carboxylic acid 4-(4-trifIuoromethy!-phenoxy)pheny! ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate. and 1-cydoheptylpiperazine. The crude product was partitioned between dichlorormethane and aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound. White crystals, 1H NMR (MeOH-cf4): 8 Two AB-systems: 7.68 - 7.58 (d-like, 2H) and 7.23 - 7.04 (m, 6H); 3.86 - 3.50 (br d, 4H), 2.98 - 2.66 (br, 5H), 2.04 - 1.37 (m, 12H); HPLC-MS m/z = 463 (M+H); IR (KBr): v 1730,1707 crrf1.
Example 300 (General procedure 15)
4-Cyclohexylpiperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 1-cyclohexylpiperazine, yield 80 %. White crystals, m.p. 290 - 291 °C, 1H NMR (DMSO-cf6): S10.82 (br s, 1H), 2 AB-systems: 7.83 -7.69 (d-like, 2H) and 7.32 - 7.10 (m, 6H); 4.40 -4.02 (br, 2H), 3.75 - 3.39 (br, 4H), 3.31- 2.98 (br, 3H), 2.23 - 2.02 (m, 2H), 1.92 - 1.74 (m, 2H), 1.70 - 0.97 (mf 6H); HPLC-MS m/z = 449 (M+H); IR (KBr): v 1717 (C=0) cm"1.
Example 301. (General procedure 15)

4-(4-ChIorobenzyI)piperazine-1-carboxylic acid 4-(4-trifluoromethyIphenoxy)phenyi ester
The hydrochloride of the title compound was prepared from 4-(4-
trffluoromethylphenoxy)phenyl chloroformate and 1-(4-chlorobenzyI)piperazine, yield 86 %. White crystals, rap. 232 - 234 °C; 1H NMR (DMSO-cf6): 8 11.92 (br s( 1 H)r 3 AB-systems: 7.83 - 7.62 (Hike, 4H) and 7.62 - 7.48 (d-like, 2H). and 7.32 - 7.07 (m, 6H); 4.51 - 3.95 (br s at 4.37 ppm overlapping with br signal at 4.2 ppm, 4H), 3.95 - 2.95. (br m, 9H: 6H + water); IR (KBr): v 1717 (C=0)crrf1.
Example 302 (General procedure 15)
4-(4~Methylbenzy!)piperazine-1-carboxylic acid 4-(4-trifluorornethylphenoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 1-(4-methyIbenzyI)piperazine, yield 96 %. White crystals, m.p. 250-252°C; HPLC-MS m/z = 472 (M+H); IR (KBr): v 1720 (C=0) cm-1.
Example 303 (General procedure 15)
4-(4-Methoxybenzyl)piperazine-1 -carboxylic acid 4-(54rifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title, compound was prepared from 4-(5-trifIuoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-methoxybenzyI)piperazine, yield 78 %. White crystals, m.p. 237 - 238 °C; HPLOMS m/z = 488 (M+H); IR (KBr): v. 1719 (C=0) cm'1.
Example 304 (General procedure 15)
4-(2-Chloro-6-fluoro-benzyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-chloro-6-fluorobenzyl)piperazine. White crystals, m.p. 204 - 205 °C (from ethanol); HPLC-MS m/z = 510 (M+H); (R (KBr): v 1726 (C=0) cm"1;
Example 305 (General procedure 15)
4-(3-Methoxyphenyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester

The hydrochloride of the title compound was prepared from 4-(4-trffluoromethylphenoxy)phenyl chloroformate and 1-(3-methoxyphenyI)piperazine. White crystals, m.p. 168-171 °C (sinters at 160 °C); HPLC-MS m/z = 473(M+1); IR (KBr): v 1739, 1716(C=0)cm~1.
Example 306 (General procedure 15)
4-Benzyl-piperazine-1-carboxylic acid 4-(3-chloro-5-trifIuoromethyl-pyridin-2-yIoxy)phenyI ester
The hydrochloride of the title compound was prepared from 4-(3-chIoro-5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-benzyl-piperazine, yield 94 %. White crystals; m.p. 111-113 °C (resolidifies) and 114-115 °C; HPLC-MS m/z = 492 (M+H).
Example 307 (General procedure 8)Methy!-phenyl-carbamic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy~4-iodopyrazoIe and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, oil). 1H NMR (300MHz; CDCI3): 8 3.44 (bs, 3H), 7.30-7.48 (m, 7H).; HPLC-MS : m/z = 343.9 (M+1);R« = 4.12min.
Example 308 (General procedure 8)Methyi-phenyl-carbamic acid benzotriazol-1-yl ester
The title compound was prepared from 1-hydroxybenzotriazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, crystallizes slowly). 1H NMR (300MHz; CDCI3): S 3.50 (bs, 3H), 7.37-7.57 (m, 8H), 8.04 (d, 1H).; HPLC-MS: mlz = 269.0 (M+1); Rt = 3.69 min.
Example 309 (General procedure 8)Methyl-phenyl-carbamic acid [1,2,3]triazolo[4,5-b]pyridin-3-yl ester
The title compound was prepared from [l^spYiazolofrS-^pyridin-S-ol and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified

by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, oil).
1H NMR (300MHz; CDCI3): 5 3.50 (bs, 3H), 7.30-7.60 (m, 6H), 8.40. (d, 1H), 8.75 (d, 1H);
HPLC-MS: m/z = 270.0 (M+1); Rt = 3.18 min.
Example 310 (General procedure 8)MethyI-pheny!-carbamic acid 3-(2-nitro-phenyI)-pyrazol-1-yI ester
The title compound was prepared from 1-hydroxy-3-(2-nitrophenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (94%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 6.44 (bs, 1H), 7.30-7.50 (m, 7H), 7.58 (dt, 1H), 7.72-7.78 (m, 2H); HPLC-MS : mlz= 339.1 (M+1); Rt = 4.15 mln.
Example 311 (General procedure 8)Methyl-phenyl-carbarnic acid 3-(4-nitro-phenyI)-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-3-(4-nitrophenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, yellow crystals). 1H NMR (300MHz; CDCI3): 5 3.47 (bs, 3H), 6.70 (bd, 1H), 7.32-7.50 (m, 6H), 7.94 (d, 2H), 8.26 (d, 2H); HPLC-MS : m/z= 339.1 (M+1); Rt = 4.41 min.
Example 312 (General procedure 8)Methyl-phenyl-carbamic acid 3-pyridin-2-yl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-pyridyI)pyrazoIe and N-methyl-N-phenylcarbamoyl chloride, applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, oil). 1H NMR (300MHz; CDCI3): S 3.48 (bs, 3H), 6.95 (d, 1H), 7.20 (dd, 1H), 7.30-7.48 (m, 6H), 7.70 (dt, 1H), 7.93 (d, 1H), 8.61 (d, 1H); HPLC-MS : m/z= 295.1 (M+1); Rt = 2.75 min.
Example 313 (General procedure 8)Methyl-phenyl-carbamic acid 3-thiophen-2-yl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-thienyI)pyrazole and N-methyl-N-

phenyicarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (66%, oil). 1H NMR (300MHz; CDCI3): S 3.46 (bs, 3H), 6.48 (bd, 1H), 7.03 (dd, 1H), 7.25 (dd, 1H), 7.30-7.48 (m, 7H); HPLC-MS : mlz = 300.1 (M+1); Rt = 4.16 min..
Example 314 (General procedure 8)MethyI-phenyI-carbamic acid 3-(2-fluoro-phenyI)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3-(2-fIuorophenyi)pyrazoIe and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil). 1H NMR (300MHz; CDCI3): 8 3.48 (bs, 3H), 6.75 (bt, 1H), 7.07-7.47 (mf 9H), 7.97 (dt, 1H); HPLC-MS : mlz = 312.1 (M+1); Rt = 4.45 min.
Example 315 (General procedure 8)Methyl-phenyl-carbamic acid 3-bromo-pyrazoi-1-y! ester
The title compound was prepared from 1-hydroxy-3-bromopyrazo!e and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil).
1H NMR (300MHz; CDCI3): 8 3.43 (bs, 3H), 6.31 (d, 1H), 7.26-7.48 (m, 6H).; HPLC-MS : mlz = 298.0 (M+1); Rt= 3.97 min.
Example 316 (General procedure 8)Methyl-phenyI-carbamic acid 5-iodo-pyrazol-1-y! ester
The title compound was prepared from 1-hydroxy-5-iodopyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (64%, oil).
1H NMR (300MHz; CDCI3): 8 3.48 (bs, 3H), 6.42 (df 1H), 7.28-7.47 (m, 6H).; HPLC-MS : mlz = 343.9 (M+1); Rt= 3.81 min.
Example 317 (General procedure 8)Methyl-phenyl-carbamic acid 2-chloro-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-chloroimidazoIe, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (77%, oil).
1H NMR (300MHz; CDC!3): 8 3.45 (bs, 3H), 6.90 (bs, 1H)f 7.07 (bs, 1H), 7.35-7.40 (m, 3H),
7.46 (bt, 2H); HPLC-MS : mlz = 251.9 (M+1); Rt = 3.29 min.
Example 318 (General procedure 8)Methyl-phenyl-carbamic acid 4-(4-methoxy-phenyI)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-4-(4-methoxyphenyI)pyrazo!e and N-methy!-N-phenylcarbamoyt chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (6%, oil). 1H NMR (300MHz; CDCI3): 5 3.45 (bs. 3H), 3.82 (s, 3H)( 6.90 (d, 2H), 7.30-7.48 (m, 7H), 7.54 (bs, 2H); HPLC-MS : mlz= 346.1 (M+23); R( = 4,16 min.
Example 319 (General procedure 8)Methy!-phenyl-carbarnic acid 5-benzoyI-pyrazoI-1-yI ester
The title compound was prepared from 1-hydroxy~5-benzoy]pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (30%, crystals). 1H NMR (300MHz; CDCI3): S 3.48 (bs, 3H), 6.69 (bs, 1H), 7.27-7.52 (m, 8H), 7.63 (t, 1H), 7.79 (d, 2H); HPLC-MS: mlz = 344.0 (M+23); Rt = 4.41 min.
Example 320 (General procedure 8)Methyl-phenyl-carbamic acid 5-(4-methoxy-phenyl)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-5-(4-methoxyphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (38%, yellow crystals).
1H NMR (300MHz; CDCI3): 8 3.33 (bs, 3H), 3.86 (s, 3H), 6.34. (d, 1H), 6.95 (d, 2H), 7.25-7.45 (m, 8H); HPLC-MS: mlz = 324.1 (M+1); Rt = 4.27 min.
Example 321 (General procedure 8)Methyl-phenyI-carbamic acid 5-(4-dimethyiamino-phenyl)-pyrazol-1-yl ester

The title compound was prepared from 1-hydroxy-5-(4-dimethylaminophenyl)-pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (27%, crystals). 1H NMR (300MHz; CDCI3): 8 3.02 (s, 6H). 3.35 (bs, 3H), 6.30 (d, 1H), 6.72 (d, 2H), 7.30-7.46 (m, 8H); HPLC-MS : m/z= 337.1 (M+1); Rt = 4.11 min.
Example 322 (General procedure 8)Methyl-phenyl-carbamic acid 4,5-diiodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4,5-diiodopyrazole and N-methy!-N-phenylcarbamoyl chloride applying the genera! procedure 8. The. crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (76%, crystals). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 7.30-7.50 (m, 6H).; HPLC-MS : mlz = 369.9 (M+1); Rt = 4.56 min.
Example 323 (General procedure 8)MethyI-phenyl-carbamic acid 5-thiophen-2-yl-pyrazol-1-yi ester
The title compound was prepared from 1-hydroxy-5-(2-thienyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8, The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (51%, crystals). 1H NMR (300MHz; CDCI3): 8 3.44 (bs, 3H), 6.45 (bs, 1H), 7.09 (dd, 1H), 7.26 (bs, 1H); 7.28-7.49 (m, 7H); HPLC-MS : m/z= 300.1 (M+1); Rt = 4.18 min.
Example 324 (General procedure 8)MethyI-phenyl-carbamic acid 2-(4-methoxy-phenyI)-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-(4-methoxyphenyI)imidazole, hydrochloride and N-methyl-N-phenylcarbamoyI chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, crystals).
1H NMR (300MHz; CDCI3): 8 3.33 (bs, 3H), 3.86 (s, 3H), 6.92 (d, 2H), 7.04 (d, 1H), 7.10 (bs, 1H), 7.28 (d, 2H), 7.34-7.50 (m, 3H), 7.60 (bd, 2H); HPLC-MS: m/z= 324.1 (M+1); Rt = 2.87 min.

Example 325 (General procedure 8)MethyI-phenyl-carbamic acid 2-methylsulfanyI-imidazoI-1-yl ester
The title compound was prepared from 1-hydroxy-2-methylsulfanyI-imidazole hydrochloride and N-methyl-N-phenylcarbamoyi chloride applying the general procedure 8, The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil). 1H NMR (300MHz; CDC!3): S 2.56 (s, 3H), 3.44 (bs, 3H), 7.00 (bs, 1H), 7.08 (bs, 1H), 7.32-7.49 (m, 5H); HPLC-MS : miz = 264.1 (M+1); Rt = 2.99 mln.
Example 326 (General procedure 8)MethyI-phenyI-carbamic acid 3,5-bis-(4-methoxy-phenyl)-pyrazo!-1-yI ester
The title compound was prepared from 1-hydroxy-3,5-bis-(4-methoxyphenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (29%, beige crystals). 1H NMR(300MHz; CDC!3): 5 3.35 (bs, 3H), 3.84 (s, 3H)F 3.88 (s, 3H), 6.57 (s, 1H), 6.92 (d, 2H), 6.97 (d, 2H), 7.25-7.48 (m, 7H)t 7.74 (d, 2H); HPLC-MS : miz = 881.2 (2M+23); Rt = 5.26 min.
Example 327 (General procedure 8)MethyI-phenyI-carbamic acid 4-(4-fIuoro-phenyl)-5-(4-methoxy-phenyl)-3-(4-methylphenyl)-pyrazol-1 -yl ester
The title compound was prepared from 1-hydroxy-4-(4-fluoropheny!)-5-(4-methoxyphenyI)-3-(4-methylphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the. general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (11%, crystals).
1H NMR (300MHz; CDCI3): S 2.32 (s, 3H), 3.32 (bs, 3H), 3.83 (s, 3H), 6.87 (d, 2H), 6.93 (d, 2H), 7.12-7.48 (m, 13H); HPLC-MS : m/z= 530.2 (M+23); Rt = 6.04 min.
Example 328 (General procedure 8)Methyl-phenyl-carbamic acid 4-benzyl-5-(4-methoxy-phenyl)-3-(methylphenyl)-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-benzyI-5-(4-methoxyphenyl)-3-(4-methylphenyOpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-

heptane) (14%, oil).
1H NMR (300MHz; CDCI3): S 2.31. (s, 3H), 3.31 (bs, 3H), 3.83 (s, 3H), 3.95 (s, 2H), 6.89 (d,
2H), 7.08-7.39 (mt 13H), 7.43 (d, 2H); HPLC-MS : mfz = 504.2 (M+1); Rt = 6.11 min.
Example 329 (General procedure 8)Methyl-phenyl-carbamic acid 4-acetyl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-acetyIpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the genera! procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, oil). 1H NMR (300MHz; CDCI3): S 2.44 (s, 3H), 3.44 (bs, 3H), 7.32-7.48 (m, 5H), 7.78 (bs, 1H)( 7.85 (bs, 1H).
Example 330. (General procedure 8)Methyl-phenyl-carbamic acid 2-(4-nitro-phenyI)-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-(4-nitrophenyI)imidazole, hydrochloride
and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude
product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, yellow
crystals).
1H NMR (300MHz; CDCI3): 5 3.38 (bs, 3H), 7.16 (s, 1H), 7.20 (s, 1H), 7.31 (d, 2H), 7.38-7.61
(m, 3H), 7.86 (bs, 2H), 8.25 (d, 2H).
Example 331 (General procedure 8)Methyl-phenyl-carbamic acid 2-chloro-5-(4-methylphenyl)-imidazol-1 -yl ester
The title compound was prepared from 1-hydroxy-2-chloro-5-(4-methylphenyl)imidazole, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (80%, oil).
1H NMR (300MHz; CDCI3): 8 2.40 (s, 3H), 3.33 (bs, 3H), 7.00 (s, 1H), 7.19-7.29 (m, 6H), 7.35-7.50 (m, 3H).
Example 332 (General procedure 8)MethyI-phenyl-carbamic acid 4-formyl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-formylpyrazole and N-methyl-N-

phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (73%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 7.29-7.50 (m, 5H), 7.84 (bs, 1H), 7.90 (bs, 1H), 9.83 (s, 1H).
Example 333 (General procedure 8)Methyl-phenyl-carbamic acid 4-hydroxymethyl-pyrazoI-
1-yI ester
The title compound was prepared from 1-hydroxy-4-hydroxymethylpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, oil). *H NMR (300MHz; CDCI3): 8 2.33 (bs, 1H), 3.40 (bs, 3H), 4.50 (s, 2H), 7.28-7.46 (m, 7H).
Example 334 (General procedure 8)Methyl-phenyl-carbamic acid 4-phenylethynyI-pyrazol-1-yi ester
The title compound was prepared from 1-hydroxy-4-phenyIethynyIpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (40%, yellow crystals). 1H NMR (300MHz;. CDCI3): 8 3.42 (bs, 3H), 7.30-7.58 (m, 12H).
Example 335 (General procedure 8)Methyl-phenyl-carbamic acid 2-bromo-imidazol-1-yl ester
The title compound was prepared from l-hydroxy-2-bromoimidazole, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 6.98 (bd, 1H), 7.11 (bs, 1H), 7.33-7.50 (m, 5H); HPLC-MS : mlz = 296.0 (M+1); Rt = 2.90 min.
Example 336 (General procedure 8)Methyl-phenyl-carbamic acid 2-phenylsulfanyl-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2- phenylsulfanylimidazole hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude

product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (61%, oil). 1H NMR (300MHz; CDC!3): 8 3.35 (s, 3H), 7.12 (bd, 1H), 7.17-7.39 (m, 11H); HPLC-MS : m/z= 326.0 (M+1); Rt = 3.65 min.
Example 337 (General procedure 8)Morpholine-4-carboxylic acid imidazoI-1-yl ester
The title compound was prepared from 1-hydroxyimidazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by preparative HPLC (water-acetonitriIe-0.1%TFA) (36%, crystals).
1H NMR (300MHz; CDCI3): 8 3.57 (bs, 2H), 3.66 (bs, 2H), 3.78 (t, 4H), 7.12 (bs, 1H), 7.15 (bt, 1H), 7.90 (s, 1H); HPLC-MS : m/z= 198.1 (M+1); Rt= 0.36 min.
Example 338 (General procedure 8)MorphoIine-4-carboxyIic acid 2-bromo-imidazol-1-yI ester
The title compound was prepared from 1-hydroxy-2-bromoimidazole, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (98%, crystals). 1H NMR (300MHz; CDCI3): 8 3.60 (bs, 2H), 3.71 (bs, 2H), 3.80 (t, 4H), 7.02 (d, 1H), 7.18 (d, 1H); HPLC-MS : m/z = 276.0 (M+1); Rt = 1.73 min.
Example 339 (General procedure 8)Morpholine-4-carboxylic acid 2-chloro-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-chloroimidazoIe, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (54%, oil).
1H NMR (300MHz; CDCI3): 8 3.58 (bs, 2H), 3.68 (bs, 2H), 3.69 (t, 4H), 6.94 (d, 1H), 7.10 (d, 1H); HPLC-MS : mlz = 232.0 (M+1); Rt = 1.69 min.
Example 340 (General procedure 8)Morpholine-4-carboxylic acid 2-phenylsulfanyl-irnidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-phenylsulfanylimidazole, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc) (98%, oil).
1H NMR (300MHz; CDCI3): S 3.46 (bs, 4H)f 3.66 (bs, 4H), 7.15 (d, 1H). 7.18-7.31 (m, 6H);
HPLC-MS : mlz* 306.1 (M+1); Rt = 2.75 min.
Example 341 (General procedure 8)Morpholine-4-carboxyIic acid 2-(4-methoxy-phenyI)-imidazol-1-yl ester
The title compound was prepared from 14iydroxy-2-(4-methoxypheny!)imidazole, hydrochloride and 4-morphoIine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (49%, crystals). 1H NMR (300MHz; CDCI3): 8 3.51 (bs, 2H), 3.62-3.76 (m, 6H), 3.86 (s, 3H), 6.96 (d, 2H), 7.08 (d, 1H), 7.11 (d, 1H), 7.70 (d, 2H); HPLC-MS : m/z= 304.1 (M+1); Rt= 1.81 min.
Example 342 (General procedure 8)Morpholine-4-carboxylic acid 4-bromo-pyrazol-1-yI ester
The title compound was prepared from 1-hydroxy-4-bromopyrazoIe and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (85%, crystals).
1H NMR (300MHz; CDCI3): 5 3.57 (bs, 2H), 3.68 (bs, 2H), 3.79 (t, 4H), 7.35 (d, 1H), 7.43 (d, 1H); HPLC-MS :m/z= 298.0 (M+23); Rt= 2.46 min.
Example 343 (General procedure 8)Morpholine-4-carboxylic acid 4-iodo-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, crystals).
1H NMR (300MHz; CDCl3): 5 3.56 (bs, 2H), 3.66 (bs, 2H), 3.77 (t, 4H), 7.41 (d, 1H), 7.44 (d, 1H); HPLC-MS : mfz = 324.0 (M+1); Rt = 2.65 min.
Example 344 (General procedure 8)Morpholine-4-carboxylic acid 3,4,5-tribromo-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3,4,5-tribromopyrazole and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, crystals).

1H NMR (300MHz; CDCI3): S 3.59 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H); HPLC-MS : mlz = 455.6 (M+23); Rt= 3.91 min.
Example 345 (General procedure 8)
Morpholine-4-carboxylic acid 3-(4-methoxy-phenyl)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3-(4-methoxyphenyI)pyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, crystals). 1H NMR (300MHz; CDCI3): 5 3.58 (bs, 2H), 3.71 (bs, 2H), 3.79 (t, 4H), 3.84 (s, 3H), 6.53 (d, 1H), 6.92 (d, 2H), 7.40 (d, 1H), 7.71 (d, 2H); HPLC-MS : /n/z= 326.0 (M+23); Rt = 3.21 min.
Example 346 (General procedure 8)MorphoIine-4-carboxylic acid 3-thiophen-2-yi-pyrazoi-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-thienyI)pyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (75%, crystals).
1H NMR (300MHz; CDCl3): 8 3.57 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H), 6.51 (d, 1H), 7.04 (dd, 1H), 7.26 (dd, 1H), 7.34 (dd, 1H)f 7.40 (d, 1H); HPLC-MS : mlz = 280.0 (M+1); Rt = 3.12 min.
Example 347 (General procedure 8)MorphoIine-4-carboxyIic acid pyrazol-1-yl ester
The title compound was prepared from 1-hydroxypyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (94%, crystals).
1H NMR (300MHz; CDCI3): S 3.57 (bs, 2H), 3.69 (bs, 2H)t 3.79 (t, 4H), 6.32 (t, 1H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS: mlz = 198.0 (M+1); Rt = 1.18 min.
Example 348 (General procedure 16)4-Methyl-piperazine-1-carboxy!ic acid pyrazoM-yl ester
The title compound was prepared from 1-hydroxypyrazole and N-methylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (water-acetonitrile-0.1% TFA) (17%, salt with TFA).

1H NMR (300MHz; CDCl3): 8 2.36 (s, 3H), 2.50 (bt, 4H), 3.59 (bs, 2H), 3.71 (bs, 2H), 6.31 (t, 1H), 7.38 (dd, 1H), 7.40 (dd, 1H); HPLC-MS : mlz =211.0 (M+1); Rt = 0.40 min.
Example 349 (General procedure 16)4~CyclopentyI-piperazine-1-carboxyIic acid pyrazoM-yl ester
The title compound was prepared from 1-hydroxypyrazoIe and N-cycIopentylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (wa-ter-acetonitrile-0.1 % TFA) (34%, salt with TFA).
1H NMR (300MHz; CDCI3): 8 1.45-2.01 (m, 8H), 2.70 (bs, 4H), 2.92 (bs, 1H), 3.55 (bt, 1H), 3.63 (bs, 2H), 3.77 (bs, 2H), 6.31 (t, 1H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : m/z = 265.1 (M+1); Rt= 0.54 min.
Example 350 (General procedure 16)4-Phenyi-piperazine-1-carboxylic acid pyrazoI-1-y! ester
The title compound was prepared from 1-hydroxypyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals).
1H NMR (300MHz; CDCI3): 8 3.25 (bt, 4H), 3.72 (bs, 2H), 3.85 (bs, 2H), 6.33 (t. 1H), 6.92-6.98 (m, 3H), 7.27-7.33 (m, 2H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : mlz = 273.1 (M+1); ' Rt = 3.06 min.
Example 351 (General procedure 16)4-Pyridin-2«yI-piperazine-1-carboxylic acid pyrazol-1-yl ester
The title compound was prepared from 1-hydroxypyrazole and 1-(2-pyridyI)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (59%, crystals).
1H NMR (300MHz; CDCI3): 8 3.62-3.85 (m, 8H), 6.32 (t, 1H), 6.66-6.72 (m, 2H), 7.39 (dd, 1H), 7.42 (dd, 1H), 7.53 (dt, 1H), 8.21 (d, 1H); HPLC-MS : m/z= 274.1 (M+1); Rt = 0.63 min.
Example 352 (General procedure 16)4-Pyrimidin-2-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester

The title compound was prepared from 1-hydroxypyrazole and 1-(2-pyrimidyI)piperazine ap- . plying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (57%, crystals).
1H NMR (300MHz; CDCI3): 8 3.65 (bs, 2H). 3.78 (bs, 2H), 3.95 (bs, 4H), 6.32 (t, 1H), 6.5S (t, 2H), 7.38 (dd, 1H), 7.42 (dd, 1H), 8.35 (d, 1H); HPLC-MS : mlz= 275.2 (M+1); Rt = 2.14 min.
Example 353 (General procedure 16)4-Benzo[1,3]dioxoI-5-yI-piperazine-1-carboxylic acid pyrazol-1-yI ester
The title compound was prepared from 1-hydroxypyrazole and 1-Benzo[1,3]dioxol-5-ylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (92%, crystals).
1H NMR (300MHz; CDCI3): 8 3.11 (bt, 4H), 3.71 (bs, 2H), 3.83 (bs, 2H), 5.93 (s, 2H), 6.32 (t, 1H), 6.39(dd, 1H),6.57(d, 1H), 6.74(d, 1H), 7.37 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : mlz = 317.2 (M+1); Rt = 2.96 min.
Example 354 (General procedure 16)4-BenzyI-piperazine-1~carboxy!ic acid 4-iodo-pyrazoI-l-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-benzylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (32%f oil).
1H NMR (300MHz; CDCI3): 8 2.53 (bs, 4H), 3.57 (bs, 4H), 3.67 (bs, 2H), 7.28^7.38 (m, 5H)f 7.40 (d, 1H), 7.43 (d, 1H); HPLC-MS : m/z = 413.0 (M+1); Rt = 1.75 min..
Example 355 (General procedure 16)4-Cydopentyl-piperazine-1-carboxylic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazoIe and N-cyclopentylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane-3% Et3N) (61%, crystals). 1H NMR (300MHz; CDCI3): 8 1.33-1.94 (m, 8H), 2.46-2.61 (m, 5H), 3.57 (bt, 2H), 3.67 (bt, 2H), 3.63 (bs, 2H). 3.77 (bs, 2H), 7.40 (d, 1H), 7.44 (d, 1H); HPLC-MS : m/z= 391.1 (M+1); Rt= 1.31 min.

Example 356 (General procedure 16)4-(4-Fluoro-benzyI)-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-(4-fluorobenzy!)piperazine applying the genera! procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals). 1H NMR (300MHz; CDCI3): S 2.50 (t, 4H), 3.51 (s, 2H), 3.57 (bt, 2H), 3.66 (bt, 2H), 7.02 (t, 2H), 7.29 (dd, 2H), 7.40 (d, 1H), 7.43 (d, 1H); HPLC-MS : m/z= 431.0 (M+1); Rt = 1.79 min.
Example 357 (General procedure 16)4-PhenyI-piperazine-1-carboxyIic acid 4-iodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (52%, crystals).
1H NMR (300MHz; CDCI3): S 3.25 (t, 4H), 3.72 (bs, 2H), 3.81 (bs, 2H), 6.90-6.97 (m, 3H), 7.30 (t, 2H), 7.41 (d, 1H), 7.47 (d, 1H); HPLC-MS : m/z= 399.1 (M+1); Rt = 3.91 min.
Example 358 (General procedure 16)4-Pyridin-2-y!-piperazine-1-carboxyIic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-(2-pyridyI)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (45%, crystals).
1H NMR (300MHz; CDCI3): S 3.62-3.82 (m, 8H), 6.66-6.72 (m, 2H), 7.42 (d, 1H), 7.47 (d, 1H), 7.54 (dtf 1H), 8.22 (d, 1H); HPLC-MS : m/z = 400.0 (M+1); Rt = 1.47 min.
Example 359 (General procedure 16)4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4-iodo-pyrazoH-yl ester
The. title compound was prepared from 1-hydroxy-4-iodopyrazole and 1~(2-pyrimidyl)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (10%, crystals). 'H NMR (300MHz; CDCI3): 5 3.62 (bs, 2H), 3.72 (bs, 2H), 3.95 (bs, 4H), 6.58 (t, 2H), 7.41 (d, 1H), 7.46 (d, 1H), 8.36 (d, 1H); HPLC-MS : mlz = 401.0 (M+1); Rt = 3.09 min.

Example 360 (General procedure le^Benzotl^ldioxol-S-yl-piperazine-l-carboxylic acid 4-iodo-pyrazoi-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-Benzo[1,3]dioxol-5-ylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (59%, crystals).
1H NMR (300MHz; CDCI3): 5 3.11 (t, 4H), 3.69 (bs, 2H)( 3.80 (bs, 2H), 5.92 (s, 2H), 6.38 (dd, 1H), 6.56 (d, 1H), 6.73 (d, 1H), 7.41 (d, 1H), 7.45. (d, 1H); HPLC-MS : m/z= 443.0 (M+1); Rt, = 3.79 min.
Example 361
4-(1-EthylpropyI)piperazine-1-carboxyIic acid 3-trifluoromethylphenyl ester hydrochloride salt
To a stirred mixture of 1-(1-ethyIpropyI)piperazine (175//1,1.0 mmol) and dry DCM (10 m!) was added 3-trifluoromethylphenyl chloroformate (250 mg, 1.1 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the residue was dissolved in a 0.5 N HCI solution (15 m!) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 330 mg (86 %) of the title compound as a solid. M.p. 260-261°C.
1H NMR (400 MHz, DMSO-d6): 8 0.98 (t, 6H), 1.63 (hept, 2H), 1.86-1.98 (m, 2H), 3.03-3.12 (m, 1H), 3.12-3.31 (m, 2H), 3.41-3.49 (m, 2H), 3.52-3.85 (m, 2H), 4.05-4.35 (m, 2H), 7.47-7.70 (m, 4H),11.0(brs,1H).
Example 362
4-(1-Ethylpropyl)piperazine-1-carboxyIic acid naphthalen-1-yl ester hydrochloride salt
To a stirred mixture of 1-(1-ethylpropyl)piperazine (175 //1,1.0 mmol) and dry DCM (10 ml) was added 1-napthalenyl chloroformate (225 mg, 1.1 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the residue was dissolved in a 0.5 N HCI solution (15 ml) and a small portion of acetonitrile. The acidic : solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and

dried to give 310 mg (85 %) of the title compound as a solid.
M.p. 288-290°C.
1H NMR (400 MHz, DMSO«d6): 8 1.00 (t, 6H), 1,63 (hept, 2H), 1.86-2.02 (m, 2H), 3.07-3.18 (m, 1H), 3.18-3.42 (m, 2H), 3.42-3.55 (m, 2H), 3.55-3.73 (m, 1H), 3.78-3.95 (m, 1H), 4.05-4.25 (m, 1H), 4.35-4.55 (m, 1H), 7.35 (d, 1H), 7.53 (t, 1H), 7.56-7.7.61 (m,,2H), 7.85 (d, 1H), 7.90-8.05 (m, 2H), 10.75 (brs,1H).
Example 363
4-(1-EthylpropyI)piperazine-1-carboxyIic acid 4-fluorophenyl ester hydrochloride salt
To a stirred mixture of 1-(1-ethylpropyI)piperazine (350 //I, 2.0 mmo!) and dry DCM (15 ml) was added 4-fluorophenyl chloroformate (350 mg, 2.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the residue was re-evaporated twice with acetonitrile to give 590 mg of the free base. The hydrochloride salt was prepared from 465 mg free base by addition of a 0.5 N HCI solution (15 ml) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 470 mg (90 %) of the title compound as a solid.
M.p. 275-277°C.
1H NMR (400 MHz, DMSO-d6): 5 0.98 (t, 6H), 1.64 (hept 2H), 1.85-1.95 (m, 2H), 3.02-3.11 (m, 1H), 3.11-3.28 (m, 2H), 3.38-3.46 (m, 2H), 3.50-3.80 (m, 2H), 4.00-4.30 (m, 2H), 7.18-7.26 (m, 4H), 10.85 (brs,1H).
Example 364
4-(1-Ethylpropyl)piperazine-1-carboxyIic acid 2-nitrophenyl ester hydrochloride salt
To a stirred mixture of 1 -(1 -ethylpropyl)piperazine (175 //1,1.0 mmol) and dry DCM (10 ml) was added 2-nitrophenyl chloroformate (201 mg, 1.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the residue was dissolved in a 0.5 N HCI solution (15 ml). The acidic solution was concentrated and

stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 310 mg (86 %) of the title compound as a solid.
M.p. 251-253°C.
1H NMR (400 MHz, DMSO-d6): 8 0.96 (t, 6H), 165 (hept, 2H), 1.83-1.95 (m, 2H), 3.06-3.25 (m, 3H), 3.42-3.53 (m, 2H), 3.53-3.83 (m, 2H), 4.02-4.13 (m, 1H), 4.20-4.34 (m, 1H), 7.50-7.55 (m, 2H), 7.83 (t, 1H), 8.13 (d, 1H), 10.9 (brs, 1H).
Example 365 4-(1-EthylpropyI)piperazine-1-carboxylic acid 4-methoxycarbonylpheny! ester hydrochloride salt
To a stirred mixture of 1-(1-ethylpropy!)piperazine (350 ;/!, 2.0 mmol) and dry DCM (15 ml) was added 4-methoxycarbonylphenyI chloroformate (430 mg, 2.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and re-evaporated twice with acetonitrile. The residue was dissolved in a 0.5 N HCI solution (15 ml) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 670 mg (90 %) of the title compound as a solid.
M.p. 248°C decomp.
1H NMR (400 MHz, DMSO-d6): 8 0.97 (t, 6H), 1.63 (hept, 2H), 1.85-1.95 (m, 2H), 3.02-3.11 (m, 1H), 3.11-3.30 (m, 2H), 3.40-3.48 (m, 2H), 3.50-3.80 (m, 2H)P 3.85 (s, 3H), 4.05-4.33 (m, 2H), 7.33 (d, 2H), 8.00 (d, 2H)), 10.7 (brs, 1H).
Example 366
Methyl-phenyl-carbamic acid 5-(3,3-dimethyl-butyrylamino)-pyridin-2-yl ester
A solution of N-(6-hydroxy-pyridin-3-yl)-3,3-dimethyl-butyramide (0.42 g, 2.00 mmol), N-methyl-N-phenylcarbamoyl chloride (0.37 g, 2.20 mmol) and 1,4-diazabicyclo[2,2,2]octane (0.25 g, 2.20 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature for 2.5 hours. Water was added and the solution was extracted three times with dichloromethane.. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo.

The residue was redissotved in ethyl acetate and the solution was filtered over a short pad of siiicagel. Evaporation of the solvent and crystallisation of the solid from ethyl acetate:heptane yielded the title compound (0.54 g, 79% yield) as a white solid.
1H NMR (300MHz, CDCI3): 8 = 1.03 (s, 9H), 2.15 (s, 2H), 3.47 (br.s, 3H), 6.91 (br.s, 1H), 7.27 (m, 1H)f 7.38 (m, 4H), 7.99 (br.s + dd, 2H), 8.13 (d, 1H); HPLC-MS (Method A): m/z = 342 (M+H)+; Rt = 3.67 min.
Example 367
Methyl-phenyl-carbamic acid 5-[(pyridine-2-carbonyI)-amino]-pyridin-2-yI ester
A solution of pyridine-2-carboxylic acid (6~hydroxy-pyridin-3-yi)-amide hydrochloride (0.50 g, 1.99 mmol), N-methyl-N-phenylcarbamoyI chloride (0.44 g, 2.59 mmol) and 1,4-diazabicyclo[2,2,2]octane (0.54 g, 4.81 mmol) in dimethylformamide (15 mL) was stirred at room temperature for 1 hour. Water was added and the solids were isolated by suction, re-dissolved in dichloromethane. The solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 50:50) yielding the title compound (0.38 g, 55% yield) as a white solid. 1H NMR (300MHz, CDCI3): 5 = 3.45 (br.s, 3H), 7.11 (br.s, 1H), 7.26 (m, 1H), 7.40 (d, 4H), 7.51 (m, 1H), 7.92 (dt, 1H), 8.28 (d, 1H), 8.45 (dd, 1H), 8.60 (m, 2H), 10.10 (s, 1H); HPLC-MS (Method A): m/z = 349 (M+H)+; Rt = 3.31 min.
Example 368
Methyl-phenyl-carbamic acid 2-(4l4-dimethyI-2,6-dioxo-piperidin-1-yI)-pyrimidin-5-yl ester
A solution of 1«(5-hydroxy-pyrimidin-2-yI>4»4-dimethyl-piperidine-2,6-dione (0.60 g, 2.55 mmol), N-methyl-N-phenylcarbamoyI chloride (0.48 g, 2.81 mmol) and 1,4-diazabicyclo-[2,2,2]octane (0.31 g, 2.81 mmol) in dichloromethane (25 mL) was stirred at room temperature for 15 minutes. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02l ethyl acetate:heptane 50:50), yielding the title compound as a white solid.
1H NMR (300MHz, CDCI3): 8 = 1.22 (s, 6H), 2.65 (s, 4H), 3.44 (br.s, 3H), 7.28-7.48 (m, 5H), 8.68 (br.s, 2H); HPLC-MS (Method A): m/z = 369 (M+H)+; Rt = 3.45 min.
Example 369
Methyl-phenyl-carbamic acid 5-bromo-pyrimidin-2-yI ester

A mixture of 4-bromo-2-hydroxypyrimidine (0.96. g, 5.49 mmol), N-methyl-N-phenylcarbamoyl chloride (1.02 g, 6.04 mmol) and 1 ,4-diazabicyclo[2,2,2]octane (0.68. g, 6.04 mmol) in dry tet-rahydrofuran (15mL) was stirred at room temperature for 1 hour. Dichloromethane was added and the solution was extracted twice with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo yielding the title compound (170 g, 100% yield) as a white solid.
1H NMR (300MHz, CDCI3): 8 = 3.43 (br.s, 3H), 7.27 (m, 1H), 7.38 (m, 4H), 8.68 (br.s, 2H); HPLC-MS (Method A): m/z = 330 and 332 (M+H)+; Rt = 3.33 min.
Example 370
Methyl-phenyl-carbamic acid 5-[(6-chloro-pyridine-3-carbonyI)-amino]-pyridin-2-yl ester
A mixture of 4-chIoro-N-(6-hydroxy-pyridin-3-y!)-nicotinamide (0.56 g, 2.25 mmol), N-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00. mmol) and 1,4-diazabicyclo[2,2,2]octane (0.67 g, 6.00 mmol) in dry tetrahydrofuran (15mL) was stirred at room temperature for 1 hour. Dichloromethane was added and the solution was extracted twice with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate;heptane 70:30) followed by crystallised from ethyl acetate:heptane, yielding the title compound (44 mg, 5% yield) HPLC-MS (Method A): m/z = 383 (M+H)+; Rt = 3.40 min.
Example 371
Methyl-phenyl-carbamic acid 5-(2,2-dimethyl-propylcarbamoyl)-pyridin-2-yl ester
A solution of N-(2,2-dimethyl-propyI)-6-hydroxy-nicotinamide (0.50 g, 2.40 mmol), N-methyl-N-phenylcarbamoyl chloride (0.41 g, 2.40 mmol) and 1,4-diazabicyclo[2,2,2]octane (0.27 g, 2.40 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature for 3 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (first column: Si02, dichloromethane:ethyl acetate 95:5, second column: Si02) ethyl acetate), yielding the title compound (0.43 g, 52% yield).
1H NMR (300MHz, CDCI3): 5 = 0.97 (s, 9H), 3.26 (d, 2H), 3.44 (br.s, 3H), 6.26 (br.s, 1H), 7.08 (br.s, 1H), 7.29 (m, 1H), 7.39 (m, 4H), 8.13 (br.d, 1H), 8.70 (br.s, 1H); HPLC-MS (Method A): m/z = 383 (M+H)+; Rt = 3.40 min.

Example 372
[Methyl-phenyl-carbamic add 6-(3,4-clichloro-phenoxy)-pyridazin-3-yl ester
A solution of 6-(3,4 Example 373
4-(tert-Butyl-dimethyI-silanyIoxy)-piperidine-1-carboxyiic acid 5-benzoyiamino-pyridin-2-yl
ester
A solution of N-(6-hydroxy-pyridin-3-yI)-benzamide (214 mg, 1.00 mmol), 3-[4-(tert-butyl-dimethyl-silanyIoxy)-piperidine-1-carbonyI]»1-methyI-3H-imidazol-1-ium iodide (451 mg, 1.00 mmol) and 1,4-diazabicyclo[2,2,2]octane (112 mg, 1.00 mmol) in dimethylformamide (10 mL) was stirred for 18 hours at room temperature followed by heating for 3 days at 40 °C. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 40:60), yielding the title compound (364 mg, 77% yield) 1H NMR (300MHz, CDCI3): 5 = 0.08 (s, 6H), 0.91 (s, 9H), 1.59 (m, 2H), 1.78 (m. 2H), 3.50 (m, 1H), 3.62 (m, 2H), 3.76 (m, 1H). 4.00 (m, 1H), 6.87 (d, 1H), 7.41 (m, 2H), 7.50 (m, 1H), 7.90 (d, 2H), 8.01 (dd, 1H), 8.36 (d, 1H), 9.03 (sf 1H, NH); HPLC-MS (Method A): m/z = 456 (M+H)+; Rt = 5.23 min.
Example 374
4-Hydroxy-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester
Hydrofluoric acid (min. 40% in water, 0.50 mL) was added to a stirred solution of 4-(tert-butyl-dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester (364 mg, 0.77 mmol) in acetonitrile. After stirring overnight at room temperature the solvent was evaporated in vacuo. The residue was redissolved in dichloromethane. After addition of triethylamine (1 mL) the solution was filtered over a short pad of silicagel and washed with ethyl acetate:acetone 50:50. Evaporation of the solvent yielded the title compound (180 mg,

68% yield) as a white solid.
1H NMR (400MHz. CDCI3 + DMSO-d6): 8. = 1.60. (m, 2H), 191 (m, 2H), 3.25. (m, 2H), 4.02 (m, 1H), 4.41 (d, 1H), 7.07 (d, 1H). 7.44-7.61 (m, 3H), 7.99 (m, 2H), 8.35 (ddf 1H), 8.72 (d, 1H), 10.19 (s, 1H, NH); HPLC-MS (Method A): m/z = 342 (M+H)+; Rt = 2.37 min.
Example 375
4-Hydroxy-piperidine-1-carboxylic acid 5-trifIuoromethyI-pyridin-2-yl ester
A solution of 2-hydroxy-5-trifluoromethyIpyridine (0.32 g, 2.00 mmol), 4-(tert-butyl-dimethyK siianyloxy)~piperidine-1-carboxyIicacid 5-benzoylamino-pyridin-2-yI ester (0.90 g, 2.00 mmol) and triethylamine (0.20 g, 2.00 mmol) in acetonitrile (10 mL) was stirred at room temperature for three days. Hydrofluoric acid (min. 40% in water, 0.50 mL) was added and stirring was continued for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 75:25), followed by crystallisation from ethyl acetate'.heptane, yielding the title compound (0.27 g, 47% yield) as a white solid. 1H NMR (300MHz, CDCI3): S = 1.64 (m, 3H, 2 x CH + OH), 1.96 (m, 2H)f 3.33 (m, 1H), 3.45 (m, 1H), 4.00 (m, 3H), 7.27 (d, 1H)f 8.00 (dd, 1H), 8.64 (dt 1H); HPLC-MS (Method A): m/z = 313 (M+Na)+;Rt = 2.45 min.
Example 376
4-Hydroxy-piperidine-1-carboxylic acid 5-(4-chloro-benzoylamino)-pyridin-2-yI ester
A solution of 4-chloro-N-(6-hydroxy-pyridin-3-yI)-benzamide (0.50 g, 2.00 mmol), 4-(tert-butyl-dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin«2-yl ester (0.90 g, 2.00 mmol) and triethylamine (0.20 gf 2.00 mmol) in dimethylformamide (10 mL) was stirred overnight at room temperature. The solvent was evaporated in vacuo. The residue was dissolved in dichloromethane, filtered over a short pad of silicagel and washed with ethyl ace-taterheptane 50:50. The solvent was evaporated in vacuo and the residue was redissolved in acetonitrile. and hydrofluoric acid (min. 40% in water, 0.50 mL) was added. After stirring overnight at room temperature the solvent was evaporated in vacuo. Dichloromethane and triethylamine (1 mL) were added and the solution was extracted twice with water, dried over sodium sulphate, filtered and evaporated in vacuo. Crystallisation from ethyl acetate:heptane yielded the title compound (321. mg, 43% yield).
1H NMR (300MHz, DMSO-d6): 5 = 1.50 (m. 2H), 1.80 (m, 2H), 3.16 (m, 1H), 3.31 (m, 1H), 3.75 (m, 2H), 3.88 (m, 1H), 4.81 (d, 1H), 7.18 (d, 1H), 7.62 (d, 2H), 8.01 (d, 2H), 8.24 (dd,

1H), 8.66 (d, 1H), 10.58 (s, 1H).; HPLC-MS (Method A): m/z = 376 (M+H)+; Rt = 2.81 min.
Example 377
4-Hydroxy-piperidine-1-carboxyIic acid 5-(3-methoxy-benzoylamino)-pyridin-2-yl ester
Starting fromN-(6-hydroxy-pyridin-3-y!)-3-methoxy-benzamide (0.49 g, 2,00 mmol) and using the procedure as described in Example 376 yielded the title compound (347 mg, 47% yield). 1H NMR (300MHz, CDCI3 + DMSO-d6): 8 = 1.51 (m, 2H), 1.82 (m, 2H), 3.16 (m, 1H), 3.30 (m, 1H), 3.79 (s, 3H + m, 2H), 3.92 (m, 1H), 4.28 (br.s, 1H), 6.98 (m, 2H), 7.30 (t, 1H), 7.47 (m, 2H), 8.24 (dd, 1H), 8.64 (d, 1H), 10.04 (s, 1H); HPLC-MS (Method A): m/z = 372 (M+H)+; Rt = 2.58 min.
Example 378
4-Hydroxy-piperidine-1-carboxylic acid 5-(4-methoxy-benzoylamino)-pyridin-2-yl ester
Starting from N-(6-hydroxy-pyridin-3-yI)-4-methoxy-benzamide (0.49 g, 2.00 mmol) and using the procedure as described in Example 376 yielded the title compound (297 mg, 40% yield). 1H NMR (300MHz, CDC!3): 5 = 1.61 (m, 2H), 1.92 (m, 2H), 3.25 (m, 1H), 3.39 (m, 1H), 3.89 (s, 3H + m, 3H), 4.03 (m, 1H), 6.96 (d, 2H), 7.06 (d, 1H), 7.98 (d, 2H), 8.34 (dd, 1H), 8.67 (d, 1H), 9.72 (s, 1H); HPLC-MS (Method A): m/z = 372 (M+H)+; Rt = 2.53 min.
Example 379
4-Hydroxy-piperidine-1-carboxylic acid 5-(2,4-dichloro-benzoyiamino)-pyridin-2-yl ester
Starting from 2,4-dichloro-N»(6-hydroxy-pyridin-3-yl)-benzamide (0.49 g, 2.00 mmol) and using the procedure as described in Example 376 yielded the title compound (367 mg, 45% yield).
1H NMR (300MHz, CDCI3): 5 = 1.62 (m, 2H), 1.90 (m, 2H), 3.24 (m, 1H), 3.39 (m, 1H), 3.88 (m, 3H), 4.01 (m, 1H), 7.03 (d, 1H), 7.32 (d, 1H), 7.47 (s, 1H), 7.53 (d, 1H)( 8.28 (ddf 1H), 8.58 (d, 1H), 10.1. (s, 1H); HPLC-MS (Method A): m/z = 410 and 412 (M+Hf; Rt = 2.99 min.
Example 380
4-Hydroxy-piperidine-1-carboxylic acid 5-(4-trifluoromethyl-benzoylamino)-pyridin-2-yl ester
Starting from N-(6-hydroxy-pyridin-3-yI)-4-trifluoromethyl-benzamide (0.56 g, 2.00 mmol) and

using the procedure as described in Example 376 yielded the title compound (367 mg, 45% yield).
1H NMR (300MHz, CDCfe): 8 = 1.61 (m, 2H), 1.93 (m, 2H). 3.27 (mf 1H), 3.41. (mf 1H), 3.67 (br.s, 1H)f 3.91. (mf 2H), 4.05 (m, 1H)( 7.08 (d, 1H), 7.74 (d, 2H)f 8.14 (d, 2H), 8.37 (dd, 1H)f 8.67 (d, 1H)f 10.11 (s, 1H); HPLC-MS (Method A): m/z = 410 (M+H)+; Rt = 3.18 min.
Example 381
4-Hydroxy-piperidine-tearboxyIicacM^^ [1 .fflbipyridinyl-S'-yl ester
A solution of 6i-hydroxy-4l4-dimethyl-4t5-dihydro-3H-[1I3,]bipyridInyl-2,6-dione (468 mg, 2.00 mmol), 4-(tert-butyl-dimethyI-siIanyloxy)-piperidine-1-carboxi/[ic acid 5-benzoylamino-pyridin-2-yI ester (0.90 g, 2.00 mmol) and triethylamine (0.20 g, 2.00 mmol) in dimethylformamide (10 mL) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo. The residue was dissolved in ethyl acetate, filtered over a short pad of siiicagei and washed with ethyl acetate. The solvent was evaporated in vacuo and the residue was dissolved in 1N HCI in ethyl acetate (10 mL, 10.0 mmol). After stirring for 1.5 hours at room temperature the solvent was evaporated in vacuo. The white solid was washed with a small amount of ethyl acetate and diethyl ether and dissolved in a few millilitres of dichloromethane and triethylamine (1 mL). Purification by flash column chromatography (Si02, ethyl acetate:acetone 90:10) yielded the title compound (182 mg, 25% yield) as a white solid. 1H NMR (300MHz, CDCi3): 5 = 1.22 (s, 6H), 1.61 (m, 2H), 1.92 (m, 2H). 2.70 (s, 4H), 3.28 (m, 1H), 3.40 (m, 1H), 3.63 (d, 1H), 3.84-4.08 (m, 3H), 7.21 (d, 1H), 7.51 (dd, 1H), 8.07 (d, 1H); HPLC-MS (Method A): m/z = 362 (M+H)+; Rt = 2.25 min.
Example 382
Methyl-phenyl-carbamic acid 2f6-dioxo-3J4,5I6-tetrahydrO"2H-[1)3l]bipyridinyl-6,-yl ester
A solution of N-methyl-N-phenyl carbamoyl chloride (170 mg, 1.00 mmol), 6'-hydroxy-4,5-dihydro-3H-[1,3]bipyridinyl-2,6-dione (206 mg, 1.00 mmol) and 1(4-diazabicyclo[2f2,2]bctane (112 mg, 1.00 mmol) in tetrahydrofuran (10 mL) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, first ethyl acetate:heptane 75:25 followed by pure ethyl acetate). Evaporation of the solvent yielded the title compound (260 mg, 77% yield) as a white solid. 1H NMR (300MHz, CDCI3): 5 = 2,10 (quintet, 2H), 2.81 (t, 4H), 3.53 (br.s, 3H), 7.12 (br.s,

1H), 7.27 (m, 1H), 7.38 (m, 4H), 7.50 (d, 1H), 8.09 (s, 1H); HPLC-MS (Method A): m/z = 340 (M+H)+; Rt = 2.89 min.
Example 383
Methyl-phenyl-carbamic acid 5-(2,5-dioxo-pyrrofidin-1-yI)-pyridin-2-yI ester
A solution of N-methyl-N-phenyl carbamoyl chloride (170 mg, 1.00. mmol), 1-(6-hydroxy~ pyridin-3-yl)-pyrro[idine-2,5-dione (192 mg, 1.00 mmol) and 1,4-diazabicyclo[2,2,2]octane (112 mg, 1.00 mmol) in tetrahydrofuran (10 mL) was stirred at room temperature for 4 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 80:20) yielding the title compound (275 mg, 85% yield) as a white solid.
1H NMR (300MHz, CDCI3): 5 = 2.89 (s, 4H), 3.44 (br.s, 3H), 7.14 (br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.74 (br.d, 1H), 8.38 (s, 1H); HPLC-MS (Method A): m/z = 326 (M+H)+; Rt = 2.78 min.
Example 384
Methyl-phenyl-carbamic acid 5-(4-trifluoromethyl-benzoyIamino)-pyridin-2-yl ester
A solution of N-(6-hydroxy-pyridin-3-yl)-4-trifIuoromethyI-benzamide (1.41 g, 5.00 mmol), N-methyl-N-phenylcarbamoyl chloride (0.85 gf 5.00 mmol) and 1,4-diazabicyclo[2,2,2]octane (0.56 g, 5.00 mmol) in dimethylfoimamide (10 mL) was stirred at room temperature overnight . The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane 50:50) yielding the title compound (1.34 g, 64% yield) as a white solid.
1H NMR (300MHz, CDCI3): 8 = 3.35 + 3.51 (2 x br.s, 3H), 6.83 (br.s, 1H), 7.24-7.42 (m, 5H), 7.60 (d, 2H), 7.98 (d, 3H), 8.33 (s, 1H). 9.03 + 9.18 (2 x br.s, 1H, NH); HPLC-MS (Method A): m/z = 416 (M+H)+; Rt = 4.14 min.
Example 385
Methyl-phenyl-carbamic acid quinolin-6-yl ester
A solution of 6-hydroxyquinoline (1.00 g, 6.89 mmol), N-methyl-N-phenylcarbamoyl chloride (1.17 g, 6.89 mmol) and 1,4-diazabicyc!o[2,2r2]octane (0.77 gf 6.89 mmol) in dichloro-methane (20 mL) was stirred at room temperature for 1.25 hours. More dichloromethane was

added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetaterheptane 50:50). Evaporation of the solvent and recrystalllised from ethylacetate/heptane yielded the title compound (1.33 g, 69% yield) as a white solid.. *H NMR (300MHz, CDCI3): 5 = 3.48 (s, 3H), 7.22-7.64 (m. 8H), 8.09 (d, 2H), 8.87 (m, 1H); HPLC-MS (Method A): m/z = 279 (M+Hf; Rt = 2.56 min.
Example 386
4-Hydroxy-piperidine-1-carboxylic acid 5-(5-trifluoromethy!-pyridin-2-yloxy)-pyridin-2-y! ester
A solution of 5-(5-trifluoromethyl-pyridin-2-yloxy)-pyridin-2"Ol (180 mg, 0.70 mmol), 3-[4-(tert-butyl 1H NMR (300MHz, CDCI3):8 1.63 (m, 2H), 1.79 (br.s, 1H, OH), 1.97 (m, 2H), 3.31 (m, 1H), 3.43 (m, 1H), 3.89-4.12 (m, 3H), 7.09 (d, 1H), 7.18 (d, 1H), 7.62 (ddf 1H), 7.94 (dd, 1H), 8.23 (d, 1H), 8.39 (d, 1H); HPLC-MS (Method A): m/z = 384 (M+H)+; Rt = 3.00 min.
Example 387
4-Hydroxy-piperidine-1-carboxylic acid 5-(3,5-dichloro-pyridin-2-yloxy)-pyridin-2-yl ester
Starting from 5-(3,5-dichloro-pyridin-2-yloxy)-pyridin-2-ol (265 mg, 1.03 mmol) and using the procedure as described in Example 386 yielded the title compound (121 mg, 54% yield) as a thick oil.
1H NMR (300MHz, CDCI3): 8 = 1.62 (m, 2H), 1.94 (m, 2H), 3.06 (br.s, 1H), 3.28 (m, 1H), 3.41 (m, 1H), 3.90 (m, 2H), 4.01 (m, 1H), 7.18 (d, 1H), 7.62 (dd, 1H), 7.79 (d, 1H), 7.94 (d, 1H), 8.22 (d, 1H).; HPLC-MS (Method A): m/z = 384 (M+H)+; Rt = 3.35 min.
i

Example 388
Methyi-phenyl-carbamic acid 5-(4-chlorobenzoyIamino)-pyridin-2-yl ester
A solution of 4-chloro-N-(6-hydroxy-pyridin-3-yI)-benzamide (0.50 g, 2.01 mmol), N-methyl-N-phenylcarbamoyl chloride (0.34 g, 2.01 mmo!) and 1,4-diazabicyclo[2,2,2]octane (0.22 g, 0.34 mmbl) in dimethylformamide (10 mmol) was stirred at room temperature for 2 hours. Water (100 mL) was added and a thick oil was being formed. The water was decanted and the residue dissolved in dichloromethane, dried over sodium sulphate, filtered and evaporated in vacuo. Ethyl acetate was added and the solution was heated briefly (some of the compound does not dissolve). The solvent was decanted and heptane was added to it. After standing overnight, the crystals were isolated by suction, washed with heptane and dried in a vacuum oven at 45 °C. Further purification by flash column chromatography (Si02, ethy! ace-tate:heptane 50:50), yielded the title compound (0.41 g, 53% yield) as a white solid. 1H NMR (300MHz, CDCl3): 8 = 3.38 (br.s, 3H), 6.84 (br.s, 1H), 7.20-7.42 (m, 7H),*7.80 (d, 2H), 7.97 (dd, 1H), 8.32 (df 1H), 9.09 (br.s, 1H); HPLC-MS (Method A): m/z = 382 (M+H)+; Rt = 3.63 min.
Example 389
4 Methyi-phenyl-carbamic acid 5-(4-methoxy-benzoylamino)-pyridin-2-yl ester
A solution of N-(6-hydroxy-pyridin-3-yl)-4-methoxy-benzamide (1.22 g, 5.00 mmol), N-methyl-N-phenylcarbamoyl chloride (0.85 g, 5.00 mmol) and 1,4-diazabicycIo[2,2,2]octane (0.56 g, 5.00 mmol) in dimethylformamide (20 mL) was stirred at room temperature for 2 hours. Water (100 mL) was added. The solids were isolated by suction and washed with water. Crystallisation from ethyl acetaterheptane yielded the title compound (1.08 g, 57% yield). 1H NMR (300MHz, CDCI3): 5 = 3.42 (br.s, 3H), 3.86 (s, 3H), 6.89 (d, 2H + br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.84 (d, 2H)f 8.11 (dd, 1H), 8.34 (d, 1H), 8.51 (br.s, 1H); HPLC-MS (Method A): m/z = 378 (M+H)+; Rt = 3.55 min.
Example 390
Methyi-phenyl-carbamic acid 4,4-dimethyl-3,4T5,6-tetrahydro-2H-[1,3lbipyridinyl-6,-yl ester
Asolution of 4,4-dimethyl-3I4,5I6-tetrahydro-2H-[1,3]bipyridinyl-6,-ol (0.86 g, 4.17 mmol), N-methyl-N-phenylcarbamoyl chloride (0.71 g, 4.17 mmol) and 1 ,4-diazabicycIo[2f2,2]octane (0.47 g, 4.17 mmol) in dichloromethane (10 mL) was stirred at room temperature for 2 hours.

Extra dichloromethane was added and the solution was washed with water, dried over sodium sulphate, filtered and evaporated in vacuo. Crystallisation from ethyl acetaterheptane yielded the title compound (0.58 g, 41% yield)
1H NMR (300MHz, CDCi3): 5. = 0.99 (s, 6H), 1.52 (m, 4H), 3.16 (m, 4H), 3.43 (br.s, 3H), 6.92 (br.d, 1H), 7.20-7.41 (m, 6H), 7.98 (d, 1H); HPLC-MS (Method A): m/z = 340 (M+H)+; Rt = 4.21 min.
Example 391
Methyl-phenyl-carbamic acid 2-methyl-quinoIin-6-yl ester
A solution of 2-methyIquinoIin-6-o! (1.00 g, 6.28 mmol), N-methyl-N-phenylcarbamoyI chloride (1.07 g, 6.28 mmol) and l^-diazabicyclop^^octane (0.70 g, 6.28 mmol) in dichloromethane (10 mL) was stirred at room temperature for 18 hours. Extra dichloromethane was added and the solution was extracted twice with water, dried over sodium sulphate and filtered. Some ethyl acetate and heptane were added and the solution was slowly evaporated in vacuo yielding the title compound (1.64 g, 89% yield) as a white solid. 1H NMR (300MHz, CDCI3): 5 = 2.71 (s, 3H), 3.45 (br.s, 3H), 7.25 (m, 2H), 7.40 (mf 5H), 7.54 (s, 1H), 7.98 (t, 2H); HPLC-MS (Method A): m/z = 293 (M+H)*; Rt =2.16 min.
Example 392 (General procedure 17){2-[4-(Methy!-phenyl-carbamoyloxy)-ph6nyI]-ethy!}-carbamic acid tert-butyl ester
Tyramin was N-Boc protected as described in J. Org. Chem, 49,1984,1016. To a solution of the N-Boc protected tyramin (10 mmol) in CH2CI2 (50 mL) was added N-methyl-N-phenylcarbamoyl chloride (15 mmol) and DABCO (15 mmol) at room temperature. The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%) and brine. The organic phase was separated, dried (MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 MeOH-CH2CI25:95) to give 3.45 g (93%) of the title compound as colorless crystals. HPLC-MS: mlz = 393.4 (M+Na); Rt = 4.44 min.
Example 393 (General procedure 17)Methyl-phenyl-carbamic acid 4-(2-amino-ethyi)phenyl ester
{2-[4-(Methyl-phenyl-carbamoyloxy)-phenyI]-ethyl}-carbamic acid tertbutyl ester(3.7 g; 10

mmol) from above was dissolved in CH2CI2 (90 mL). Addition of TFA (6 mL) and stirring for 4 h. The reaction mixture was evaporated to dryness and dried in vacuo at 50 °C overnight producing the title compound as a TFA salt in quantitative yield as yellow hygroscopic crystals. HPLC-MS : /n/za 271.1 (M+1); Rt = 2.17 min.
Example 394 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(toIuene-4-sulfonylamino)-ethyl]-phenyl ester
The title compound was prepared in 39% yield as a clear oil using toluenesulfony! chloride as
the aryl suffonyl chloride.
HPLC-MS : m/z= 425.2 (M+1); Rt = 4.33 min..
Example 395 (General procedure 17)MethyI-phenyl-carbamic acid 4-[2-(5-dimethylamiho-naphthalene-1 -sulfonylamino)-ethy!]-phenyI ester
The title compound was prepared in 29% yield as a yellow fluorescent oil using 5-dimethylamino-naphthalene-1-suIfonyI chloride as the aryl sulfonyl chloride. HPLC-MS : m/z= 505.1 (M+1); Rt = 4.58 min.
Example 396 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(3,4-difluoro-benzenesulfonylamino)-ethyl]-phenyl ester
The title compound was prepared in 40% yield as a clear oil using 3,4-difIuoro-benzenesulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z= 447.1 (M+1); R, = 4.47 min.
Example 397 (General procedure 17)2-{2-[4-(Methyl-phenyl-carbamoyloxy)-phenyl]-ethylsulfamoyI}-benzoic acid methyl ester
The title compound was prepared in 30% yield as an oil using 2-chlorosulfonyl-benzoic acid methyl ester as the aryl sulfonyl chloride. HPLC-MS : mlz = 469.1 (M+1); Rt = 4.37 min.
Example 398 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(2f5-dichloro-

thiophene-3-sulfonylamino)-ethyl]-phenyI ester
The title compound was prepared in 39% yield as an oil using 2,5-dichIoro-thiophene-3-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : mlz = 487.0 (M+1); Rt = 4.80 min.
Example 399 (General procedure 17)MethyI-phenyI-carbamic acid 4-[2-(5-pyridin-2-yl-thiophene-2-su!fonylamino)-ethyl]-phenyl ester
The title compound was prepared in 12% yield as crystalls using 5-pyridin-2-yl-thiophene-2-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z = 494.0 (M+1); Rt = 4.42 min.
Example 400 (General procedure 17)MethyI-phenyl-carbamlc acid 4-[2-(1-methyl-1H-imidazole-4-sulfonylamino)-ethyl]-phenyI ester
The title compound was prepared in 42% yield as a yellow oil using 1-methyl-1H-imidazole-4-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS :mlz = 415.1 (M+1); Rt = 3.31 min.
Example 401 (General procedure 17)MethyI-phenyl-carbamic acid 4-[2-(5-chloro-1,3-dimethyl-1H-pyrazol^4-sulfonyIamino)-ethyI]«phenyl
The title compound was prepared in 22% yield as an oil using 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z= 463.1 (M+1); Rt = 3.91 min.
Example 402 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(4~nitro-benzenesulfonylamino)-ethyI]-phenyl ester
The title compound was prepared in 25% yield as a yellow oil using 4-nitro-benzenesulfonyI chloride as the aryl sulfonyl chloride. HPLC-MS: mlz = 456.0 (M+1); Rt = 4.19 min.
Example 403 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(6-chloro-

imidazo[2,1 -b]thiazole-5-sulfony!amino)-ethyI]-phenyl ester
The title compound was prepared in 18% yield as an oil using 6-chloro-imidazo[2,1-b]thiazole-5-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z = 490.9 (M+1); Rt = 3.90 min.
Example 404 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(2-trifiuoromethoxy-benzenesulfony!amino)-ethyI]-pheny! ester
The title compound was prepared in 38% yield as an oil using 2-trifluorornethoxy-benzenesulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z = 495.1 (M+1); Rt= 4.49 min.
Example 405 (General procedure 17)
Methyl-phenyl-carbamic acid 4-(2-dimethylaminosulfonylamino-ethy!)-phenyI ester
The title compound was prepared in 32% yield as an oil using dimethylaminosulfamoyl chloride as the sulfonyl chloride. HPLC-MS : m/z = 378.1 (M+1); Rt = 3.62 min.
Example 406 (General procedure 17)Methyl-phenyl-carbamic acid 4-(2-methanesulfonylamino-ethyI)-phenyl ester
The title compound was prepared in 22% yield as an oil using methanesulfony! chloride as
the sulfonyl chloride.
HPLC-MS : m/z = 349.0 (M+1); Rt = 3.26 min.
Example 407 (General procedure 17)MethyI-phenyl-carbamic acid 4-[2-(6-morpholin-4-yl-pyridine-3-sulfonylamino)-ethyI]-phenyI ester
The title compound was prepared in 55% yield as crystals using 6-morphoiin-4-yi-pyridine-3-
sulfonyl chloride as the aryl sulfonyl chloride.
HPLC-MS: m/z = 497.0 (M+1); Rt = 3.90. min.
Example 408 (General procedure 17)Methyl-phenyl-carbamic acid 4-[2-(6-phenoxy-pyridine-
3-su(fonylamino)-ethyl]-phenyl ester

The title compound was prepared in 54% yield as crystals using 6-phenoxy-pyridine-3-
sulfonyl chloride as the aryl sulfonyl chloride.
HPLC-MS : mlz = 504.4 (M+1); Rt = 4.45 min.
Example 409MethyI-phenyl-carbamic acid 4-{2-[4-(4-methyl-piperazin-1-yt)-
benzenesulfonylamino]-ethyl}-phenyl ester
To a stirred solution of 1~(4-bromophenyI)-4-methylpiperazina (2.05 g, 8.0 mmol) in THF (10 mL) was added dropwise 1.57 M solution in hexanes n-BuLi (4.6 mL, 7.2 mmol) over a 5-min
period at -78°C. The mixture was stirred at -78°C for 15 min. Then gaseous sulphur dioxide (ca. 5 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium; 4-(4-methyI-piperazin-1-y!)-benzenesulfinate was isolated by filtration under N2 (g), washed with THF (20 mL) and dried in vacuo providing 1.83 g (96%) of the lithium sulfinate as a solid. This lithium sulfinate (83 mg, 0.34 mmol) was suspended in CH2CI2 (1 mL) and stirred with NCS (45 mg, 0.34 mmol) for 10 min at rt. A solution of N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyt)phenyI ester as its TFA salt (0.26 mmol) in CH2Cl2 (1.5 mL) was added together with DIPEA (0.90 mmol). The mixture was stirred at rtfor 16 h and quenched with HOAc (2 mL) and water (2 mL). Ex- • traction with CH2CI2 and drying of the combined organic extracts gave the crude product which was purified by preparative HPLC (Gilson). This gave 54 mg (33%) of the title compound as its TFA salt as colorless crystals. HPLC-MS : mlz = 509.0 (M+1); Rt = 2.88 min.
Example 410Methy!-phenyI-carbamic acid 4-[2-(4-dimethylamino-benzenesulfonylamino)-ethyl]-phenyl ester
To a stirred solution of (4-bromo-phenyl)-dimethyIamine (4.02 g, 20 mmol) in THF (25 mL) was added dropwise 1.57 M solution in hexanes n-BuLi (11.5. mL, 18 mmol) over a 5-min period at -78°C. The mixture was stirred at -78°C for 15 min. Then gaseous sulphur dioxide (ca. 5 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium sulfinate was isolated by filtration under N2 (g), washed with THF (20 mL) and dried in vacuo providing 2.99 g (87%) of lithium; 4-dimethylamino-benzenesulfinate as a bluegreen solid. This lithium sulfinate (65 mg, 0.34 mmol) was suspended in CH2CI2 (1 mL) and stirred with NCS (45 mg, 0.34 mmol) for 10 min at rt A solution of N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyl)phenyl ester as its TFA salt (0.26 mmol) in CH2Cl2 (1.5 mL) was added together with DIPEA (0.90 mmol). The

mixture was stirred at rt for 16. h and quenched with HOAc (2 mL) and water (2 mL). Extraction with CH2CI2 and drying of the combined organic extracts gave the crude product which was purified by preparative HPLC (Gilson). This gave 37 mg (31%) of the title compound as an oil.
HPLC-MS : m/z= 454.5 (M+1); Rt = 4.16 min. Example 411
Methyl-phenyl-carbamic add 4-{2-[4-(2-pyrroIidin-1 -yI-ethoxy)-benzenesuIfonyIamino]-ethyl}-phenyl ester
To a stirred solution of 1-[2-(4-bromo-phenoxy)-ethyl]-pyrrolidine (6.72 g, 25 mmol) in THF (45 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (14 mL, 22.4 mmol) over a 5-min period at -78°C. The mixture was stirred at -78°C for 15 min. Then gaseous sulphur dioxide (ca. 6 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium sulfmate was isolated by filtration under N2 (g), washed with THF (40 mL) and dried in vacuo providing 5.04 g (78%) of lithium; 4-(2-pyrrolidin-1-yl-ethoxy)-benzenesulfinate as a solid. This lithium sulfonate (179 mg, 0.69 mmol) was suspended in CH2Cl2 (2 mL) and stirred with NCS (80 mg, 0.60 mmol) for 10 min at rt. A solution of N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyl)phenyl ester as its TFA salt (0.55 mmol) in CH2CI2 (3 mL) was added together with DIPEA (2.0 mmol). The mixture was stirred at rt for 16 h and evaporated to dryness. It was then redissolved in MeCN and purified by preparative HPLC (Gilson). This gave 89 mg (25%) of the title compound as its TFA salt as a crystals. HPLC-MS : m/z= 524.5 (M+1); Rt = 3.04 min.
Example 412 (General procedure 15)
4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-
yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(tetrahydrofuran-2-ylmethyl)-piperazinel crude yield 0.28 g (89%). The crude product was stirred with a mixture of ethyl acetate (10 ml) and a solution of sodium bicarbonate (0.05 g) in water (5 ml). The aqueous layer was extracted with ethyl acetate (10 + 5 mi), the combined organic phases were,washed with brine (5 ml), dried over sodium sulfate, filtered and evaporated. The residue was triturated with heptane (3 ml), filtered and dried to give the title compound, White crystals, m.p. 98 -100 °C; 1H NMR (CDCI3) 5

8.52 - 8.37 (br. 1H), 7.98 - 7.83 (dd, 1H). 7.25 - 7.06 (m, 4H), 7.00 (d, J = 8.5 Hz), 4.18 - 3.47 (m, 7H), 2.76 - 2.36 (m, 6H), 2.13 -1.74. (m, 3H), 1.64 -1.40 (m, 1H); 1R (KBr): v 1715 (C=0) cm"1.
Example 413 (General procedure 15)
4-CyclopropylmethyI-piperazine-1 -carboxylic acid 4-(3-chloro-54rifluoromethyI-pyridin-2-
y!oxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(3-chIoro-5-trifluoromethyl-pyridin-2-yIoxy)-phenyl chloroformate and 1-cyclopropylmethyI-piperazine, yield 83%. White crystals, m.p. 254-255°C; IR (KBr): v 1728 (C=0) cm'1.
Example 414 (General procedure 15)
4-(Tetrahydro-furan-2-ylmethyI)-piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenyi chloroformate and 1-(tetrahydro-furan-2-ylmethyl)-piperazine, yield 93%. White crystals, m.p. 216-217°C; IR (KBr): v 1730 (C=0) cm-1.
Example 415 (General procedure 15)
4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-trifluoromethyl-phenoxy)-phenyl chloroformate and 1-cyclohexyImethyl-piperazine, yield 93%. White crystals, m.p. 256-258 °C; IR (KBr): v 1715 (C=0) cm"1.
Example 416 (General procedure 15)
4-Cyclohexylmethyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2-
yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(3-chloro-5-trifluoromethyI-pyridin-2-yloxy)-phenyL chloroformate andl-cyclohexylmethyl-piperazine, yield 76%. White crystals, m.p. 265-266 °C; IR (KBr): v 1732 (C=0) cm"1.

Example 417 (General procedure 15)
4-CycIopropylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyI-phenoxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-trifluoromethyI-phenoxy)-
phenyl chloroformate and 1-cyclopropylmethyI-piperazine, yield 43%. White crystals, rap.
238-239°C; IR (KBr): v 1725 (C=0) cm"1.
Example 418 (General procedure 15)
4~(Tetrahydrofuran-2-ylmethy!)-piperazine-1 -carboxylic acid. 4-(3-chIoro-5-trifluoromethyI-
pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(3-chIoro-5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(tetrahydrofuran-2-yImethyI)-piperazine, yield 23%. White crystals, m.p. 98-100 °C; IR (KBr): v 1731 (C=0) cm-1.
Example 419 (General procedure 15)
4-Naphthalen~1-ylmethyI-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-naphthalen-1-ylmethyl-piperazine, yield 71%. White crystals, m.p. 218-219 °C; IR (KBr): v 1713 (C=0) cm"1.
Example 420 (General procedure 15)
4-(2-Cyclohexyl-ethyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifiuoromethyl-pyridin-2-yloxy)-phenyl chloroformate and H2-cyclohexyl-ethyl)-piperazine, yield 90%. White crystals, m.p. 274-276 °C; IR (KBr): v 1715 (C=0) cm'1.
Example 421 (General procedure 15)
4-(3-Methoxy-phenyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-
phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor-

mate and 1-(3-methoxy-phenyl)-piperazine, yield 96%. White solid, m.p. 109-111 GC; IR (KBr):v172l (C=0)cnT1.
Example 422 (General procedure 15)
4-CyclopropyImethyl-piperazine-1 -carboxylic acid 4-[2-(4-chloro-phenyI)-ethylcarbamoyI]-
phenyl ester
The title compound was prepared from 4-[2-(4-chloro-phenyI)-ethyIcarbamoyI]-phenyI chloro-formate and 1-cydopropyimethyI-piperazine, yield 18%. White crystals, m.p. 225-226 °C; IR (KBr): v 1710 (ester C=0), 1661 (amide OO) cm'1.
Example 423 (General procedure 15)
4-(Tetrahydro-furan-2-ylmethyI)-piperazine-1 -carboxylic acid 4-[2-(4-chloro-phenyl)-ethy!carbamoyl]-phenyI ester
The title compound was prepared from 4-[2-(4-chioro-phenyI)-ethylcarbamoyI]-phenyl chloro-formate and 1-(tetrahydrofuran-2-y!methy[)-piperazine, yield 12%. White crystals, m.p. 220-221 °C; IR (KBr): v 1708 (ester C=0), 1660(amide C=0) cm-1.
Example 424 (General procedure 15)
4-(3,4-DichIoro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-y!oxy)-phenyl chloroformate and 1-(3,4-dichloro-benzyI)-piperazine, yield 86%. White crystals, m.p. 229-230 °C; IR (KBr): v 1717 (C=0) cm'1.
Example 425 (General procedure 15)
4-Cyciopropylmethyl-[1 ,4]diazepane-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-
Example 426 (General procedure 15)
4-(2-Pyridin-2-yl-thyl)~piperazine-l -carboxylic acid 4-(5-trifIuoromethyI«pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-pyridin-2-yI-ethyl)-piperazine, yield 81%. White crystals, m.p. 281-282 °C; IR (KBr): v 1713 (C=0) cm-1.
Example 427 (General procedure 18)
4-(Pyrazin-2-yl)-piperazine-l -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title compound was prepared from 4-(5-trifIuoromethyI-pyridin-2-yloxy)-pheny! chloroformate and 1-(pyrazin-2-yl)-piperazine-White crystals, m.p. 160-161 °C; HPLC-MS; m/z = 446
(M+1) at Rt = 4.0 min.; 1H NMR (DMSO-c/6): S 8.60 - 8.57 (m, 1H), 8.39 - 8.36 (m, 1H), 8.27 -8.22 (dd-Iike, 1H), 8.14 - 8.11 (m, 1H)7.91 - 7.87 (d-like, 1H), 7.29 - 7.21 (m, 5H), 3.80 - 3.64 (brf 6H), 3.64 - 3.50 (br, 2H); IR (KBr): v 1737, 1714 (C=0) cm"1.
Example 428 (General procedure 15)
4-(Benzo-isothiazoI~3-yl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(benzo-isothiazol-3-yl)-piperazine. Drying on a rotary evaporator of the crude product gave the title compound as the free base. Purification by flash chromatography (silica, ethyl acetate - heptane 1:4) gave white crystals, m.p. 132-133 °C; IR (KBr): v 1726 (C=0) cm"1.
Example 429 (General procedure 15)
4-(5-Chloro-thiophen-2-ylmethyl)«piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-
yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin«2-yloxy)-phenyl chloroformate and 1-(5-chloro-thiophen»2-ylmethyl)-piperazine, yield 48 %. White crystals, m.p. 225 - 226 °C (from EtOH); 1H NMR (DMSO-ds): 5 12.00 (br,1H), 8.60 -i 8.55 (1H), 8.27 - 8.21 (dd-iike, 1H), 7.33 - 7.20 (m, 6H), 7.20 - 7.15 (d, 1H), 4.55 (br s, 2H),

4.40 - 4.00 (br, 2H), 3.74 - 3.27 (br, 4H + H20); 3,27 - 2.97 (br, 2H); IR (KBr): v 1723 (OO) cm"1.
Example 430 (General procedure 15)
4-(3-TrifluoromethyI-phenyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yioxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(3-trifiuoromethyl-phenyi)-piperazine. The crude product was converted to the free base, yield 56%. White crystals, m.p. 87-88 °C; !R (KBr): v 1719 (C=0) cm'1.
Example 431 (General procedure 15)
4-(5-Chloro-2-methyl-phenyf)-piperazine-1 -carboxylic acid 4~(5-trifluorometby)-pyridin-2-
yloxy)-phenyl ester
The hydrochloride of the title, compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(5-chloro-2-methy!-phenyI)-piperazine The crude product was converted to the free base, yield 26%. White crystals; HPLC-MS:m/z = 492(M+H) at Rt = 5.5 min.; IR (KBr): v 1722 (C=0) cm"1.
Example 432 (General procedure 15)
4-(1 -Methyl-piperidin-4-ylmethy()-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-
yloxy)-phenyl ester
The dihydrochloride of the title compound was prepared from4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(1-methyl-piperidin»4-ylmethyl)-piperazine, yield 6%.
White crystals, m.p. 305-306 °C; IR (KBr): v 1713 (C=0) cm-1.
Example 433 (General procedure 15)
4-Biphenyl-4-ylmethyl-[1,4]diazepane-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-biphenyl-4-ylmethyI-[1,4]diazepane. The crude product

was converted to the free base, yield 17%. White crystals, m.p. 143 °C; HPLC-MS: m/z = 548(M+H) at Rt= 3.6 min.; IR (KBr): v 1711 (OO) cm-1..
Example 434 (General procedure XX)
4-(5-DimethyIamino-naphthalene-1-sulfony!)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyi chlorofor-mate and 1-(5-dimethylamino-naphthalene»1-sulfony[)-piperazine and purified by flash chromatography (ethyl acetate - heptane 1:4), yield 32%. Pale crystals, HPLC-MS: m/z: 601 (M+1) atRt= 5.2min.;m.p. °C; !R (KBr): v 1723 (C=0) cm"1.
Example 435 (General procedure 15)
4~(3-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-y)oxy)-phenyl chloroformate and 1-(3-methoxy-benzyI)-piperazine, yield 99%. White crystals, . m.p. 214-215 °C; HPLC-MS: m/z: 489(M+1) at Rt = 2.8 min.; IR (KBr): v 1712 (C=0) cm"1.
Example 436 (General procedure 15)
4-(3-Fluoro-benzyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(3-fluoro-benzyI)-piperazine, yield 77%. White crystals, m.p. 138-139 °C; HPLC-MS: m/z: 476 (M+1) at Rt = 3.0 min.; IR (KBr): v 1714 (C=0) cm"1.
Example 437 (General procedure 18)
4-(3-Trifluoromethyl-pyridin-2-yi)»piperaane-1-carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyI chloroformate and I^S-trifluoromethyl-pyridin^-^^piperazine, yield 25%. White crystals, m.p. 131-132 °C; HPLC-MS: m/z: 513 (M+1) at Rt = 5.0 min.; IR (KBr): v 1722 (C=0) cm'1.

Example 438 (General procedure 15)
4-(3-FluorobenzyI)-piperazine-1 -carboxyiic acid 4-(4I6-dimethyl-pyrimidin-2-ylsuIfanyl)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(4,6-dimethyI-pyrimidin-2-ylsulfanyl)-phenyl chloroformate and 1-(3-fluorobenzyI)-piperazine. The crude product was converted to the free base, yield 48%. White crystals, m.p. 117-118 °C; HPLC-MS: m/z: 453 (M+1) at Rt = 2.6 min.; IR (KBr): v 1714 (C=0) cm"1.
Example 439 (General procedure 15)
5-(4-Trifluoromethoxybenzyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxy!ic acid 4-(5-trifluoromethylpyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl chloroformate and 2-(4-trifluoromethoxybenzy!)-2,5-diazabicyclo[2.2.1]heptane. The crude product was converted to the free base, yield 20%. Oil; HPLC-MS: m/z: 554 (M+1) at Rt = 3.1 min.; IR (KBr): v 1723 (OO) cm-1.
Example 440 (General procedure 18)
1-Oxo-1>t4-thiomorpholine-4-carboxylic acid 4-(5-trifIuoromethyI-pyridin-2-yIoxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yIoxy)-phenyI chloroformate and thiomorpholine 1-oxide and purified by flash chromatography (ethyl acetate), yield 37%. White crystals, m.p. 156 -157 °C; 1H NMR (CDCI3) .£8.47 - 8.40 (s-like, 1H), 7.94 -7.87 (dd-Iike, 1H), 7.24 - 7.13 (m, 4H), 7.06 - 6.99 (d-like), 4.31 - 3.91 (m, 4H), 2.97 - 2.87 -2.75 (m, 2H + 2H); IR (KBr): v 1710 (C=0) cm'1.
Example 441 (General procedure 18)
4-(2,4-Dimethoxypheny[)-piperazine-1 -carboxyiic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(2,4-dimethoxyphenyl)-piperazine. Purified by flash chromatography (ethyl acetate - heptane 1:4), yield 69%. White crystals, m.p. 98-99 °C; HPLC-MS: m/z = 504 (M+1) at

Rt = 4.0 min.; IR (KBr): v 1733,1712 (C=0) cm'1.
Example 442 (General procedure 15)
5-Benzyl-2,5-diazabicycIo[2.2. 1 ]heptane-2-carboxylic acid 4-(5-trifluoromethylpyridin-2-
yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridtn-2-yIoxy)-phenyl chloroformate and 2-benzyl-2,5-diazabicyclo[2.2.1]heptane. The crude product was converted to the free base and further purified by flash chromatography (ethyl acetate -heptane 1:4), yield 16 %. White crystals, m.p. 114-115 °C; HPLC-MS: m/z: 470 (M+1) at Rt = 2.6 min.; IR (KBr): v 1718 (C=0) cm'1.
Example 443 (General procedure 10)
4-Aminomethyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 4-aminomethylpiperidine. The crude product was purified by preparative HPLC (Method C) (32%, off-white crystals). HPLC-MS m/z = 396.1 (M+1), Rt: 2.65 min. purity: 86%.
Example 444 (General procedure 10)
4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
The' title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-pyrimidinyI)-piperazine, two equivalent of diisopropylethyiamine was added. The crude product was obtained by filtration of the reaction mixture. The crude product was washed with diethyl ether and subjected to column chromatography, ethyl acetate/heptane (1:3) (18%, white crystals). HPLC-MS m/z = 412.1 (M+1), Rt: 4.12 min.
Example 445 (General procedure 12)
4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4-(4,4-dirnethyl-2,6-dioxo-piperidin-1 -yl)-
phenyl ester
The title compound was prepared from 4-(4,4-dimethyl-2,6"dioxo-piperidin-1-yI)-phenyI chloroformate and 1-cyclopropylmethyI-piperazine, preparative HPLC (Method C) (45%, off-white crystals). HPLC-MS m/z = 400.3 (M+1), Rt 1.83 min.

Example 446 (General procedure 12)
4-(4-Methoxy-benzyI)-piperazine-1 -carboxylic acid 4-(4,4-dimethyI-2,6-dioxo-piperidin-1-yI)-
phenyl ester
The title compound was prepared from 4-(4I4-dimethyI-2,6-dioxo-piperidin-1*yI)-phenyI chloroformate and 1-(4-methoxybenzy!)-piperazine, preparative HPLC (Method C) (54%, white crystals). HPLC-MS m/z = 466.3 (M+1), Rt: 2.26 min.
Example 447 (General procedure 12)
4-Pyridin-3-ylmethyI-piperazine-1-carboxyIic acid 4-(4,4-dimethyl-2J6-dioxo-piperidin-1 -yl)-
phenyl ester
The title compound was prepared from 4-(4,4-dimethyI-2,6-dioxo-piperidin-1-y!)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine, hydrochloride, preparative HPLC (Method C) (75%, colourless oil). HPLC-MS m/z = 437.2 (M+1), Rt: 1.70 min.
Example 448 (General procedure 12)
4-(4-Methoxy-benzyI)-piperazine-1-carboxyIic acid 4-(2-cyclohexyI-acetylamino)-phenyl ester
The title compound was prepared from 4-(2-cyclohexyl-acetyIamino)-phenyI chloroformate and 1-(4-methoxybenzyl)-piperazine, preparative HPLC (Method C) (49%, white crystals). HPLC-MS m/z = 466.3 (M+1), Rt: 2.85 min.
Example 449 (General procedure 12)
4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4-(2-cycIohexyl-acetylamino)-phenyl ester
The title compound was prepared from 4-(2-cyclohexyl-acetylamino)-phenyI chloroformate and 1-cyclopropylmethyl-piperazine, preparative HPLC (methode C (60%, off-white crystals). HPLC-MS m/z = 400.3 (M+1), Rt: 2.42 min.
Example 450 (General procedure 12)
4-Pyrid»n-3-ylmethyl-piperazine-1-carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester

The title compound was prepared from 4-(2-cyclohexyl-acetyiamino)-phenyl chioroformate and 1-pyridin-3-ylmethyl-piperazine, hydrochloride, preparative HPLC (method© C) (64%, white crystals). HPLC-MS m/z = 437.4 (M+1), Rfc 2.38 min.
Example 451 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(2-cyclohexyl-ethyIsulfamoyI)-phenyl ester
The title compound was prepared from N-(2-cyclohexyI-ethyI)-4-hydroxy-benzenesulfonarnide and N-methyl-N-phenyl carbamoylchloride, preparative HPLC (Method C) (14%, light yellow oil). HPLC-MS m/z = 417.3 (M+1), Rt: 4.89 min.
Example 452 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(3-methyI-butylsulfamoyl)-phenyI ester
The title compound was prepared from 4-hydroxy-N-(3-methyl-butyl)-benzenesulfonamide and N-methyl-N-phenyl carbamoylchloride, preparative HPLC (Method C) (11%, light yellow oil). HPLC-MS m/z = 377.2 (M+1), Rt: 4.32 min.
Example 453 (General procedure 12)
(6-Methoxy-pyridin-2-yl)-methyl-carbamicacid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester
The crude product was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI chioroformate and and 2-methoxy-6-methylaminopyridine. The reaction mixture was evaporated to dryness, dissolved in dichloromethane (100 ml) and extracted with a aqueous phosphate buffer, pH 7. The aqueous phase was extracted with dichloromethane (100 ml x 2) and the combined organic phases were dryed and evaporated to dryness. The product was subjected to flash chromatography, ethyl acetate/heptane (1:7) to give the titlew product (86%, white crystals). HPLC-MS m/z = 420.4 (M+1), Rt 5.23 min.
Example 454 (General procedure 12)
4-Benamidazol-1-yI-piperidine-1-carboxyfc
ester
The crude product was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor-

mate and l-piperidine-4-yl-IH-benzimidazoIe, 5 equivalent of diisopropylamine was added, preparative HPLC (method C) (23%, colourless crystals). HPLC-MS m/z = 483.3 (M+1), Rt: 3.14. min.
Example 455 (General procedure 12)
4-Hydroxymethyl-piperidine-1-carboxylic acid 4-(2-cyclohexyI-acetylamino)-phenyI ester
The title compound was prepared from 4-(2-cyclohexyl-acetylamino)-phenyI chloroformate and 4-hydroxymethyI-piperidine, praeparative HPLC (Method C) (37%, off-white crystals). HPLC-MS m/z = 375.2 (M+1), Rt: 3.41 min.
Example 456 (General procedure 12)
4-(4-Amino-phenyI)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-y!oxy)-pheny]
ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yIoxy)-phenyl chloroformate and 4-(4-aminophenyl)piperidine, hydrochloride, praeparative HPLC (Method C) (30%, light yellow crystals). HPLC-MS m/z = 458.2 (M+1), Rt: 3.42 min.
Example 457 (General procedure 12)
4-(Methy!-pyridin-3-ylmethyl-amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-
2-yIoxy)-phenyl ester
The title compound was prepared from 4-(5-trifIuoromethyl-pyridin-2-yIoxy)-phenyl chloroformate and methyl-piperidin-4-yI-pyridin-3-ylmethyl-amine, hydrochloride, praeparative HPLC. (Method C) (31%, orange oil). HPLC-MS m/z = 487.1 (M+1), Rt: 2.64 min.
Example 458 (Genera! procedure 12)
4-(2-Oxo-pyrrolidin-1 -yl)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-piperidin-4-yI-pyrrolidine-2-one, hydrochloride, praeparative HPLC (Method C) (55%, semi-crystaline oil). HPLC-MS m/z = 450.1 (M+1), Rt: 3.81 min.

Example 459 (General procedure 12)
4-(MethyI-phenethyl-amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-
phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI chlorofor-mate and methyI-phenethyl-piperidin-4-yI-amine, hydrochloride, prasparative HPLC (Method C) (37%, colourless oil). HPLC-MS m/z = 500.1 (M+1), Rt: 3.26 min.
Example 460
4-[(Benzyl-ethyI-amino)-methyl]-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
Benzyl-ethyl-piperidin-4-yImethyI-amine (1.42 mmol) was dissolved in dichloromethane. 4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate (1.42 mmol, 0.451 g) (prepared from the corresponding phenol by conventional methods) was added at room temperature. The reaction mixture was stirred overnight and evaporated to dryness. The crude product was subjected to column chromatography, ethyl acetate/heptane (1:3) -+ Triethylamine/ethyl acetate 1:9). The fractions containing the title product, was evaporated to dryness and HCI (g) in ethyl acetate was added and stirred for 16 hours. The solution was evaporated to dryness and dryed in vacoum for 16 h. to give the title product. (58%, light yellow crystals). HPLC-MS m/z = 514.1 (M+1), Rt: 3.27 min.
Example 461 (General procedure 12)
4-[Methyl-phenethyI-amino)-methy!]-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyI ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and methyl-phenethyl-piperidin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diiso-propylamine was added, praeparative HPLC (Method C) (46%, colourless crystals). HPLC-MS m/z = 514.1 (M+1), Rt: 3.31 min.
Example 462 (General procedure 12)
4-[(CyclohexyI-methyl-amino)-methyl]«piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor-mate and cyclohexyI-methyl-piperidine-4-ylmethyI-amine, hydrochloride, 5 equivalent of diisopropylamine was added, prasparative HPLC (Method C). (43%, white crystals). HPLC-MS m/z = 492.3 (M+1), Rt 3.22 min.
Example 463 (General procedure 12)
4-[(Ethyl-pyridin-4-ylmethyl-amino)-methyI]-piperidine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyi ester
The title compound was prepared from 4-(5-trifIuoromethyl-pyridin-2-yloxy)-pheny! chlorofor-mate and ethyI-piperidin-4-ylmethyI-pyridin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopropylamine was added, prasparative HPLC (Method C) (25%, off-white crystals). HPLC-MS m/z = 515.2 (M+1), Rt: 2.77 min.
Example 464 (General procedure 12)
4-[(Benzyl-methyl-amino)-methyI]-piperidine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-
yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chlorofor-mate and benzyl-methyl-piperidin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopropylamine was added, praaparative HPLC (Method C) (56%, colourless crystals). HPLC-MS m/z = 500.2 (M+1), Rt: 3.18 min.
Example 465 (General procedure 12)
4-[(Methyl-pyrldin-3-ylmethyl-amino)-methyI]-piperidine-1 -carboxylic acid 4~(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chlorofor-mate and methyl-piperidine-4-ylmethyl-pyridine«4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopropylamine was added, praeparative HPLC (Method C) (36%, colourless crystals). HPLC-MS m/z = 501.1 (M+1), Rt: 2.74 min.
Example 466 (General procedure 12)
4-(1,3-Dihydro-isoindol-2-ylmethyl)-piperidine-1-carboxylic acid 4-(5-trifluoromethyI-pyridin-2-
yloxy)-phenyl ester

The title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chlorofor-mate and 2-piperidin-4-yImethyl-2f3-dihydro-1H-isoindole, hydrochloride, 5 equivalent of diisopropylamine was added, prseparative HPLC (Method C) (63%, colourless crystals). HPLC-MS m/z = 498.1 (M+1),. Rt: 3.07 min.
Example 467
4-BenzotriazoM -yl-piperidine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyI chlorofor-mate and 1-piperidin-4-yMH-benzotriazolef hydrochloride, 5 equivalent of diisopropylamine was added, preparative HPLC (Method C) (7%, colourless crystals). HPLC-MS m/z = 506.2 (M+1), Rt 4.56 min.
Example 468 (General procedure 12)
4-[(CyclopropylmethyI-amino)-methyI]-piperidine-1-carboxylicacid 4-(5-trifluoromthyI-pyridin-2-yIoxy)-phenyI ester
CyclopropylmethyI-piperidine-4-ylmethyi-amine (0.65 mmol, 110 mg) was dissolve in di-chloromethane. 4-(5-trifIuoromethyI-pyridin-2-yloxy)-phenyl chloroformate (0.65 mmol, 0.208 g) (prepared from the corresponding phenol by conventional methods) was added at - 15 °C for 15 min and stired at room temperature overnight and evaporated to dryness. The crude product was purified by preparative HPLC (Method C) (16%, colourless crystals). HPLC-MS m/z = 450.1 (M+1), Rt: 2.98 min.
Example 469 (General procedure 12)
4-[Methyl-(2-pyridin-2-yl-ethyl)-amino]»piperidine-1 -carboxyfic add 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title product was prepared from methyl-piperidin-4-yl-(2-pyridin-2-yl-ethyl)"amine and 4-(5-trifluoromethyl-pyridin"2-y}oxy)-phenyl chloroformate, 5 equivalent of diisopropylamine was added, preparative HPLC (method C) (48%, colourless oil). HPLC-MS m/z = 501.1 (M+1), Rt: 2.77 min.

Example 470 (General procedure 12)
4-(CyclohexyI-methyI-amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin«2-
y!oxy)-phenyl ester
The title product was prepared from cyclohexyI-methyl-piperidin-4-yl-amine, dihydrochloride and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI chloroformate, 2 equivalent of diisopro-pylamine; dimethylformamide/ tetrahydrofuran (2:1). The reaction mixture was evaporated to dryness and the crude product extracted with ethyl acetate from an aqueous HCI solution saturated with sodium chloride, pH 1-2. The title product was crystallized from ethyl acetate during evaporation of the solvent, filtered and dryed in vacoum (45%, white crystals). HPLC-MS m/z = 478.2 (M+1), Rt: 3.10 min.
Example 471 (General procedure 12)
4-(IsopropyI-methyI-amino)-piperidine-1 -carboxylic acid 4-(5-trifIuoromethyl-pyridin-2-yIoxy)-
phenyl ester
The title product was prepared from isopropyl-methyl-piperidin-4-yi-amine, dihydrochloride and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate; dimethylformamide as solvent, preparative HPLC (method C) (77%, light yellow oil). HPLC-MS m/z = 438.3 (M+1), Rt: 2.77 min.
Example 472 (General procedure 12)
(4-Methoxy-phenyl)-methyl-carbamic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyI ester
The title product was prepared from N-methyl-p-anisidine and 4-(5-trifluoromethyl-pyrldin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (61%, off-white crystals). HPLC-MS m/z = 419.2 (M+1), Rt: 4,67 min.
Example 473 (General procedure 12)
(2-Methoxy-phenyl)-methyl-carbamic add 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 2-methoxy-N-methylamine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (63%, colourless oil). HPLC-MS m/z = 419.2 (M+1), Rt 4.75 min.

Example 474 (General procedure 12)
(2-Cart3amoyl-chIoro-phenyI)-methyI-carbamic
phenyl ester.
The title product was prepared from 5-chloro-2-(methyIamino)-benzamide and 4-(5-
trifluoromethyI-pyridin-2~yloxy)-phenyI chloroformate, preparative HPLC (method C) (31%,
light yellow oil). HPLC-MS m/z = 466.1 (M+1), Rt: 3.99 min.
Example 475 (General procedure 12)
(2-CarbamoyI-phenyI)-methyI-carbamic acid 4«(5-trifluoromethyI-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 2-(methylamino)benzamide and 4-(5-trifIuoromethyI-pyridin-2-yloxy)-phenyI chloroformate, preparative HPLC (method C) (57%, light yellow oil). HPLC-MS m/z = 454.2 (M+Na), Rt: 3.66 min.
Example 476 (General procedure 12)
(2-Chloro-phenyI)-methyl-carbamic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 2-chlor-N-methylani!ine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (48%, light yellow oil). HPLC-MS m/z = 423.1 (M+1), Rt: 4.98 min.
Example 477 (General procedure 12)
(2,4-Difluoro-phenyl)-methy!-carbamic acid 4-(5-trifIuoromethyI-pyridin-2»yloxy)-phenyl ester
The title product was prepared from 2,4-difluouro-N-methyIaniIine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (37%, white crystals). HPLC-MS m/z = 425.1 (M+1), Rt: 4.90 min.
Example 478 (General procedure 12)
Methyl-(2-trifluoromethoxy-phenyI)-carbamic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl
ester
The title product was prepared from N-methyl-2-(trifluoromethoxy)-aniline and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (49%, colourless oil). HPLC-MS m/z = 473.2 (M+1), Rt 5.18 min.

Example 479 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(1,1,3,3-tetramethyI-butylcarbamoyI)-phenyI ester
The title product was prepared from tert-octylamine and 4-(methyI-pheny!-carbamoyIoxy)-benzoic acid 2,5-dioxo-pyrroiidin-1-yl ester, preparative HPLC. (method C) (26%, white crystals). HPLC-MS m/z = 383.5. (M+1), Rt: 4.67 min.
Example 480 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(2-dimethyIamino-ethyI)-methyl-carbamoyl]-phenyl ester
The title product was prepared from N.NX-trimethylethylendiamine and 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester, preparative HPLC (method C) (2%, colourless oil!). HPLC-MS m/z = 356.2 (M+1)f Rt: 2.17 min.
Example 481 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(cyclopropyImethyI-carbamoyI)-phenyI ester
The title product was prepared from cyclopropylmethylamine and 4-(methy!-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester. The crude product was used without further purification (100%, semi-crystal oil). HPLC-MS m/z = 325.1 (M+1), Rt: 3.40 min.
Example 482 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(methyl-pyridin-3-ylmethyl-carbamoyl)-phenyI ester
The title product was prepared from methyl-pyridin-3-ylmethyI-amine and 4-(methyl-phenyI-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yI ester. The crude product was subjected to preparative HPLC (method C) (48%, clear colourless oil). HPLC-MS m/z = 376.2 (M+1), Rt: 2.37 min.
Example 483 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(1H-benzimidazoI-2-ylmethyl)-carbamoyl]-phenyI ester
The title product was prepared from 0(1 H-benzimidazol-2-yI)-methyIamine and 4-(methyI-

phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroiidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (8%, off-white crystals). HPLC-MS m/z = 401.1 (M+1), Rt: 2.56 min.
Example 484 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[2-(4-chloro-pheny!)-ethylcarbamoyl3-phenyI ester
The title product was prepared from 2-(4-chIoro-phenyI)-ethyIamine and 4-(methyl-phenyI-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (39%, off-white crystals). HPLC-MS m/z = 409.2 (M+1), Rt: 4.27 min.
Example 485
4-Cyclopropy)methyI-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyI)-phenyl ester
The title product was prepared from 1-cycIopropyImethyIpiperazine (0.35 mmol) dissolved in dichloromethane (5 ml). 4-(3,3-dimethyl-butyIcarbamoyi)-phenyl chloroformate (0.35 mmol) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to . -dryness and subjected to preparative HPLC (metod C) (5%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 2.43 min.
Example 486
4-Hydroxymethy!-piperidine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyI)-phenyI ester ester
The title product was prepared from 4-hydroxymethyIpiperidtne (0,35 mmol) was dissolved in dichloromethane (5 ml). Diisopropylethylamine (0.35 mmol was added together with 4-(3,3-dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C). (25%, white crystals). HPLC-MS m/z = 363.3 (M+1), Rt 3.27 min.
Example 487
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester

The title product was prepared from 1-pyridin-3-yImethyl-piperazine was dissolved in di-chloromethane (5 ml). 4-(3,3-DimethyI-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C) (88%, light yellow oil).. HPLC-MS m/z = 425.4 (M+1),Rt 2.33 min.
Example 488
4-(4-Methoxy-benzyI)-piperazine-1-carboxyiicacid 4»(313-dimethyI-butyIcarbamoyI)-pheny! ester
The title product was. prepared from 1-(4-methoxy-benzyI)-piperazine (0.35 mmol) was dissolved in dichloromethane (5 ml). 4-(3,3-Dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmo!) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C). (54%, colourless semi-crystaline oil). HPLC-MS m/z = 454.3 (M+1), Rt: 2.78 min.
Example 489
4-(2-Pyridin-2-yl-acetyI)-piperazine-lK^rbo^ ester
a) Piperazine-I^dicarboxylicacid tert-butyl ester 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester (General procedure 18)
The title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl chloroformate and 1-tert-butoxycarbonyl-piperazin, yield 59% (recrystallized from EtOAc - heptane 1:1). White crystals, m.p. 165 -166 °C; 1H NMR (CDCI3) D 8.45 - 8.42 (m, 1H), 7.92 - 7.87 (m, dd-like, 1H), 7.21 - 7.12 (AB-system, 4H), 7.03 - 6.98 (m, d-iike, 1H), 3.72 - 3.45 (br mf 8H), 1.49 (s, 9H); 13C-NMR (CDCI3) Q (ref. CDCI3 77.00 ppm):165,71,154.56,153.51,150.21,148.34, 145.43 (q, J= 4.4 Hz), 136.701 (q, J = 3 Hz), 123.65 (q, J= 271.5 Hz), 122.86,122.24,121.62 (q, J = 33 Hz), 11.20, 80.32,44.38,43.78,44.6 - 42.3 (br), 28.36 ppm; IR (KBr) p 1722 (CO), 1691(C=0)cnrb) Piperazin&-1-carboxylic acid 4-(5-trifluoromethyl-pyridirh2-yloxy)-phenyl ester hydrochloride
Piperazine-1,4-dicarboxyIic acid tert-butyl ester 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

(0.12 g, 0.26 mmol) was stirred at 100 °Cfor 10 min in a mixture of ethanol (3 ml) and concentrated hydrochloric acid (1 ml). The solvent was removed in vacuum. The residue was stirred with toluene (10 ml) and evaporated, then stirred with ethanol and evaporated to dryness to give white crystals (0.10 g). Recrystallization from absolute ethanol gave the title compound. White crystals, 0.068 g (65%); m.p. 279 - 282 °C (decomp.); 1H-NMR (DMSO) q 9.62 (br, 2H, NH2+), 8.61 - 8.55 (m, 1H), 8.29 - 8.21 (m, dd-Iike, 1H), 7.30 - 7.20 (m, 5H), 3.86 and 3.70 (br s, 4H), 3.19 (br s, 4H); 13C-NMR (DMSO) □ (ref DMSO 39.50 ppm): 165.51,152.71,149.98,148.04, 145.20 (J = 4.4 Hz), 137.62 (J = 3.7 Hz), 123.87 (J = 271.5 Hz), 123.11,123.39, 120.39 (J = 32.2Hz), 111.80,42.15 and a broad signal partly overlapping with the DMSO signal. IR (KBr) □ 1731,1709(0=0) cm"1.
c) 4-(2-Pyridin-2-yl-acetyI)-piperazine-1-carboxytic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-pheny! ester
Triethylamine (0.026 ml) was added to a stirred solution of (pyridin-2-yI)acetic acid hydrochloride (0.033 g, 0.19 mmol) in DMF (2.5 ml) at 0 DC. 1-Hydroxy-benzotriazole containing 8% of water (0.034 g) and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.044 g) was added and the mixture was stirred for 50 min. Piperazine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester hydrochloride (0.070 g) in a mixture of DMF (1 ml) and triethylamine (0.032 ml) was added and stirring was continued over night at room temperature. The solvent was removed in vacuum and the residue was partitioned between dichloro-methane (10 ml) and water (10 ml). The organic phase was washed with water (10 ml), dried over sodium sulfate, filtered and evaporated. The residue was triturated with ether-petroleumsether 1:1 and the (2 + 1 ml). The residue was dried to give the title compound. White solid, m.p. 143 -146 °C; HPLC-MS m/z: IR (KBr) D 1732 (C=0), 1643 (C=0).
Example 490 (General procedure 15)
4-(2-Pyridin-4-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-pyridin-2-yI-ethyI)-piperazine. White crystals, m.p. 268 - 271 °C (decomp); IR (KBr) □ 2680, 2579, 2456 (N+-H), 1731,1713 (C=0) cm-1; HPLC-MS m/z: 473 (M+H) Rt = 2.3 min.

Example 491
Methyl-phenyl-carbamic acid 5-amino-pyridin-2-yI ester
A solution of methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester (10.41 g, 38.1 mmol) in tet-rahydrofuran (100 mL) was hydrogenated in a Parr apparatus with wet 5% palladium on carbon and 20 psi hydrogen pressure. After 2 hours the solution was filtered over a short pad of Celite, washed thoroughly with ethyl acetate and evaporated in vacuo, yielding title compound (9.51 g, 103% yield) as a thick oil, which solidified upon standing.
1H NMR (300MHz, CDCl3): 5 = 3.40 (br.s, 3H), 3.70 (br.s, 2H), 6.80 (br.d, 1H), 6.97 (dd, 1H), 7.22 (m, 1H), 7.36 (m, 4H), 7.72 (d, 1H); HPLC-MS (Method A): m/z = 244 (M+H)+; Rt = 2.28 min.
Example 492
Methyl-phenyl-carbamic acid 5-benzenesu]fonylamino-pyridin-2-yl ester.
Benzenesuiphonyl chloride (0.18 g, 1.00 mmol), dissolved in a small amount of dichloro-methane, was added dropwise to a stirred solution of methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester (0.24 g, 1.00 mmol) and triethylamine (0.10 g, 1.00 mmol) in dichloromethane (10 mL). After stirring for 4 hours the solution was extracted with water and evaporated in vacuo. The residue was purified by flash column chromatography (Si02l ethyl acetate:heptane 40:60 followed by 50:50) yielding the title compound (108 mg, 23% yield) as a white solid. 1H NMR (300MHzr CDCI3): 5 = 3.46 (br.s, 3H), 6.82 (br.s, 1H), 7.24-7.52 (m, 9H), 7.63 (m, 3H), 7.84 (br.s, 1H); HPLC-MS (Method A): m/z = 384 (M+H)+; Rt = 3.26 min.
Example 493
3,3-DimethyI^[6-(methykphenyk^^
A solution of methyl-phenyl-carbamic acid 5-amino-pyriditv2-yl ester (243 mg, 1.00 mmol) and
3,3-dimethylglutaric anhydride (142 mg, 1.00 mmol) in dichloromethane (10 mL) was stirred at
room temperature for 48 hours. Evaporation of the solvent yielded the title compound as a thick
oil.
HPLC-MS (Method A): m/z = 386 (M+H)+; R( = 2.76 min.
Example 494
Piperidine-1-carboxylic acid 4J4-dimethyI-2)6-dioxo-3,4,5,6-tetrahydro-2H-[1 ^bipyridinyl-e-yl

1-PiperidinecarbonyI chloride (63 microL, 0.50 mrnol) was added to a solution of B'-hydroxy^,^ dimethyl^.S^lihydrc^SH-tl^^ipyridinyl-^e-dione (117 mg, 0.50 mmol) and DABCO (56 mg, 0.50 mmol) in dimethylformamide (10 mL). After stirring for 1 hour at room temperature water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.12 g, 69% yield) as a white solid.
1H NMR (300MHz, CDCI3): 5 = 1.21 (s, 6H), 1.64 (s( 6H), 2.69 (s, 4H), 3.53 (m, 2H), 3.63 (m, 2H), 7.22 (df 1H), 7.49 (dd, 1H), 8.09 (d, 1H); HPLC-MS (Method A): m/z = 346 (M+H)+; Rt = 3.12 min.
Example 495
2,2-Dimethyl-N-[6-(methy!-phenyl-carbamoyloxy)-pyridin-3-yI]-succinamicacid
A solution of methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester (0.49 g, 2.00 mmol) and 2,2-dimethylsuccinic anhydride (0.26 g, 2.00 mmol) in dichloromethane (10 mL) was stirred at room temperature overnight Evaporation of the solvent in vacuo yielded the title compound. HPLC-MS (Method A): m/z = 372 (M+H)+; Rt = 2.84 min.
Example 496
Methyl-phenyl-carbamic add 5-(3l3-dimethyl-2l5-dioxo-pyrroIidin-1-y()-pyridin-2-y[ ester
A mixture of thionyl chloride (0.726 mL, 10.00 mmol) and 2,2-dimethyI-N-[6-(methyl-phenyl-carbamoyloxy)-pyridin"3-yI]-succinamic acid (0.74 g, 2.00 mmol) in dichloromethane (25 mL) was stirred at room temperature for 18 hours. The solvent and excess thionyl chloride were evaporated in vacuo. The crude product was redissolved in dichloromethane (25 mL) and pyridine (316 mg, 4.00 mmol) was added. The solution was extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (SiO* ethyl acetaterheptane 50:50), yielding the title compound (490 mg, 69% yield) as a white solid.
1H NMR (300MHz, CDCI3): S = 1.43 (s, 6H), 2.74 (sf 2H), 3.45 (br.s, 3H), 7.14 (br.s, 1H), 7.26 (m, 1 H)f 7.38 (m, 4H), 7.76 (br.d, 1H), 8.39. (s, 1H); HPLC-MS (Method A): m/z = 354 (M+H)+; Rt = 3.35 min.

Example 497
Methyl-phenyl-carbamic acid 5-[3,3-dimethyI-5-(4-methyI-piperazin-1 -yI)-5-oxo-pentanoy!amino]-pyridin-2-yI ester
Thionyl chloride (56 microL, 0.78 mmol) was added to a stirred solution of 3,3-dimethyl-4-[6-(methyl-phenyi-rarbamoyloxy)-pyridin-3-ylcarbamoy!]-butyric acid (0.15 g, 0.39 mmol) in di-chloromethane (5 mL) and 2 drops of dimethylformamide. After stirring for 10 minutes N-methylpiperazine (1. mL) was added and stirring was continued for 2 hours. The solvent was evaporated in vacuo. The residue was redissolved in dichloromethane and extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo. The crude product was purified by filtration over a short column (Si02, ethyl acetate followed by acetone) yielding the title compound (93 mg, 51% yield) as a thick oil.
1H NMR (300MHz, CDCI3): 5 = 1.11 (s, 6H), 2.32 (s, 3H), 2.43 (m, 8H), 3.42 (br.s, 3H), 3.61 (m, 2H), 3.74 (m, 2H), 7.00 (br.s, 1H), 7.38 (dt 4H), 8.21 (dd, 1H), 8.47 (d, 1H)f 10.90 (s, 1H); HPLC-MS (Method A): mfe = 468 (M+H)+; Rt = 2.20 min.
Example 498
Methyl-phenyl-carbamic acid 5-[3,3-dime^
ester
Thionylchloride (237 microL, 3.27 mmol) was added to a stirred solution of 3,3-dimethy!-4«[6-(methyl-phenyl-carbamoyIoxy)-pyridin-3-ylcarbamoyl]-butyric acid (0,63 g, 1.63 mmol) in dichloromethane (10 mL). After stirring for 10 minutes the solution was divided into 4 equal portions of acid chloride. To one portion was added 2-aminopyridine (0.5 mL) and after stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (SiOa, ethyl acetate followed by ethyl acetate:acetone 90:10), yielding the title compound (105 mg, 56% yield).
1H NMR (300MHz, CDCl3): 8 = 1.09 (s, 6H)f 2.36 (s, 2H), 2,38 (s, 2H), 3.44. (br.s, 3H), 6.95 (br.s, 1H), 7.26 (m, 2H), 7.38 (m, 4H), 8.05 (dd, 1H), 8.10 (dt, 1H), 8.30 (m, 2H), 8.67 (d, 1H); HPLC-MS (Method A): mfe = 462 (M+H)+; Rt = 2.52 min.
Example 499
Methyl-phenyi-rarbamic add 5-@^ yl ester

Thionylchloride (237 microL, 3.27. mmol) was added to a stirred solution of 3,3-dimethyl-4-[5-
(methyl-phenyi-rarbamoyloxy)-pyridin-3-ylcaft^ acid (0.63 g, 1.63 mmol) in di-
chloromethane (10 mL). After stirring for 10 minutes the. solution was divided into 4 equal portions of acid chloride. To one portion was added morpholine (0.5 mL) and after stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (Si02), yielding the title compound (117 mg, 63% yield).
1H NMR (300MHz, CDCI3): 5= 1.11 (s, 6H), 2.44 (s, 4H), 3.42 (br.s, 3H), 3.59 (m, 2H), 3.70 (m, 6H), 7.00 (br.s, 1H), 7.24 (m, 1H), 7.38 (d, 4H), 8.21 (dd, 1H), 8.45 (d, 1H), 10.76 (s, 1H); HPLC-MS (Method A): m/z = 455 (M+H)+; Rt = 2.87 min.
Example 500
Methyl-phenyl-carbamic acid 5-[4«(2-dimethyIamino-ethyIcarbamoyl)-3)3-dimethy!-butyrylamino]-pyridin-2-yl ester
Thionylchloride (237 microL, 3.27 mmol) was added to a stirred solution of 3r3-dimethyl-4-[6-(methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyI]-butyric acid (0.63 g, 1.63 mmol) in di-chloromethane (10 mL). After stirring for 10 minutes the solution was divided into 4 equal portions of acid chloride. To one portion was added N.N-dimethylethylenediamine (0.5 mL) and after stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (Si02), yielding the title compound (74 mg, 39% yield). 1H NMR (300MHz, CDCI3): 5 = 1.10 (s, 6H), 2.22 (s, 2H), 2.27 (s, 6H), 2.44 (m, 4H), 3.37 (m, 2H), 3.43 (br.s, 3H), 6.60 (br.t, 1H), 7.00 (br.s, 1H), 7.25 (m, 1H), 7.38 (d, 4H), 8.21 (dd, 1H), 8.46 (d, 1H), 10.70 (s, 1H); HPLC-MS (Method A): m/z = 456 (M+H)+; Rt = 1.93 min.
Example 501 (General procedure 12)
4-[Methyl-(2-pyridin-4-yI-ethyl)-amino]-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from methyI-piperidine-4-yl-(2-pyridin-4-yl-ethyl)-amine and 4-(5-trifluoramethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, preparative HPLC (method C) (15%, colourless oil). HPLC-MS m/z = 501.4 (M+1), Rt 2.04 min.
Example 502 (General procedure 12) 4-(Cyclopropyl«pyridin-4-ylmethyl-amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-

pyridin-2-yloxy)-phenyl ester
The title product was prepared from cyclopropyl-piperidine«4-yl-pyridin-4-ylmethyl-amine and 4-(5-trifIuoromethyI-pyridin-2-yIoxy)-phenyI chloroformate, 3 equivalent of diisopropylamine was added, solvent: dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (19%, yellow oil). HPLC-MS m/z = (M+1), Rt:2.82min.
Example 503 (General procedure 12)
4-[Cyclopropyl-(2-fluoro-benzyl)-amino]-piperidine-1-carboxyIicacid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from cyclopropyl-(2-fluoro-benzy[)-piperidin-4-yI-amine and 4-(5-trifIuoromethyI-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent; dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (60%, colourless oil). HPLC-MS m/z = (M+1), Rt:3.02min.
Example 504 (General procedure 12)
4-(Cyclopropyl-pyridin-3-ylmethyl«amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyI ester
The title product was prepared from cyclopropyl-piperidin-4-yl-pyridin-3-ylmethyl-amine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI chloroformate, 3 equivalent of diisopropylamine was. added, solvent: dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (26%, light brown solid). HPLC-MS m/z = (M+1) 513.3, Rt: 2.64 min.
Example 505 (General procedure 12)
4-(Cyclopropylmethyl-pyridin-3-ylmethyl-amino)-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl"pyridin-2-yloxy)-phenyl ester
The title product was prepared from cyclopropylmetiiyl-piperidin-4-yl-pyridin-3-ylmethyl-amine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (47%, off-white solid.

HPLC-MS m/z = (M+1) 513.3, Rt: 2.70 min.
Example 506 (General procedure 12)
4-(C^clopropylmethyl-pyridin-3-y!methy!-amino)-piperidine-1 -carboxylic acid 4-(5-trif!uoromethyl~pyridin-2-yloxy)-phenyl ester
The title product was prepared from cyclopropyImethyI-piperidin-4-yl-pyridin-4-ylmethy!-amine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI chloroformate, 3 equivalent of diiso-propylamine was added, solvent: dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (22%, off-white solid. HPLC-MS m/z = (M+1) 513.3, Rt: 2.70 min.
Example 507 (General procedure 12)
4-(4-Hydroxy-piperidin-1-ylmethyI)-piperidine-1-carboxyIicacid4-(5-trifiuoromethyl-pyridin«2-yloxy)-phenyl ester
The title product was prepared from 1-piperidin-4-yimethyl-piperidine-4-ol (released form the correspondent hydrochloride by a standard procedure) and 4-(5-trifluoromethyI-pyridin-2-ybxy)-phenyl chloroformate, preparative HPLC (method C) (reaction performed in a mixture of dichloromethane and dimethylformamide). 1.7 M HCI in ethyl acetate was added to the pooled fractions containing the title product, and the fractions was evaporated to dryness (92%, white solid. HPLC-MS m/z = (M+1) 480.4, Rt: 2.38 min.
Example 508 (General procedure 11)
4-{3-[1 -(2-Hydroxy-ethyi)-piperidin-4-yi]-propyI}-piperidine-1 -carboxylic acid 4-(5-
trifluoromethyl-pyridin-2-yioxy)-phenyl ester
The title product was prepared from 2-[4-(3-piperidin-4-yl-propy!)-piperidin-1-yr|-ethanol and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate. The reaction mixture was evaporated, diethyl ether (30 ml) was added and the title product isolated by filtration, washed with diethyl ether and ried to give (67%, white solid. HPLC-MS m/z = (M+1) 536.2, Rt: 3.39 min.
Example 509 (General procedure 12)
4-(2-PyrroIidin-1 -yl-ethyl}-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester

The title product was prepared from 2-[4-(3-piperidin-4-yI-propyI)-piperidin-1-yI3-ethanoI and 4-(5-trifluoromethyI-pyrJdin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C). 1.7 M HCI in ethyl acetate was added to the pooled fractions containing the title product, and the fractions was evaporated to dryness (65%, white solid). HPLC-MS m/z = (M+1) 464.1, Rt: 2.99 min.
Example 510 (General procedure 16) Methyl-o-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and methy!-o-tolylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (40%, oil). HPLC-MS : mfz = 380.1 (M+23); Rt = 4.05 min.
Example 511 (General procedure 16) Methyl-m-tolyl-carbamic acid 4-iodo-pyrazoM-yI ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and methyl-m-tolylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (44%, oil). HPLC-MS : mfz = 380.1 (M+23); Rt = 4.13 min.
Example 512 (General procedure 16) Methyl-p-tolyl-carbamic acid 4-iodo-pyrazol-l-yI ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and methyl-p-tolylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (55%, oil). HPLC-MS : mfz = 380.1 (M+23); Rt = 4.13 min.
Example 513 (General procedure 16) (3-Chloro-phenyI)-methyl-carbamic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 3-chlorophenyl-methylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (54%, oil).

HPLC-MS : mlz = 399.9 (M+23); R* = 4.28 min.
Example 514 (General procedure 16)
(3-Fluoro-phenyI)-methyl-carbamic acid 4-iodo-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy»4-iodopyrazoIe and 3-fIuorophenyl-methylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (51%, oil). HPLC-MS : mlz = 384.0 (M+23); Rt = 4.00 min.
Example 515 (General procedure 16) 4-(3-TrifluoromethyI-pyridin-2-yl)-piperazine-1-carboxyIic acid 4-iodo-pyrazol-1-yI ester
The title compound was prepared from 1-hydroxy-4-iodopyrazoie and 1-(3-trifluoromethylpyridin-2-yI)piperazine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (13%, oil). HPLC-MS : mlz = 468.1 (M+1); Rt = 4.38 min.
Example 516 (General procedure 16) 2f6-Dimethyl-morpholine-4-carboxylic acid 4-iodo-pyrazoI-1~yI ester
The title compound was prepared from 1-hydroxy-4~iodopyrazoIe and 2,6-dimethyImorphoIin. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (11%, oil). HPLOMS: mlz = 374.0 (M+23); Rt = 3.24 min.
Example 517 (General procedure 16) Thiomorpholine-4-carboxylic acid 4-iodo-pyrazoM-yI ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and thiomorpholin. The
crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (27%,
oil).
HPLC-MS: m!z= 340.0 (M+1); Rt = 3.22 min.
Example 518 (General procedure 16) 3r5-DimethyI-morpholine-4-carboxyIic acid 4-iodo-pyrazol-1-yi ester

The title compound was prepared from 1-hydroxy-4~iodopyrazole and 3,5-dimethylmorphoiin. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (15%, oil). HPLC-MS : m/z= 352.0 (M+1); Rt = 3.17 min.
Example 519 (General procedure 16) Piperidine-1-carboxy!ic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazoIe and piperidine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (46%, oil). HPLC-MS : mlz = 322.0 (M+1); Rt = 3.38 min.
Example 520 (Genera! procedure 16) Methy!-o-tolyl-carbamic acid 2-chloro-imidazo!-1-yI ester
The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and
methyl-o-tolyiamine. The crude product was purified by preparative HPLC (Gilson) (4%, red
oil).
HPLC-MS : mlz = 266.0 (M); Rt = 3.28 min.
Example 521 (General procedure 16) (3-Fluoro-phenyl)-methyl-carbamic acid 2-chloro-imidazoM-yl ester
The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and 3-fluorophenyl-methylamine. The crude product was purified by preparative HPLC (Gilson) (2%, oil). HPLC-MS : mlz = 270.1 (M); Rt = 3.08 min.
Example 522
Methyl-phenyl-carbamic acid 4-iodo-phenyl ester
To a solution of 4-iodophenol (30 mmol) in CH2CI2 (100 mL) was added N-methyl-N-phenylcarbamoyi chloride (27 mmol) and diisopropylethylamine (60 mmol) at room temperature.. The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%), aqueous Na2C03 and brine. The organic phase was dried

(MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 EtOAc-Heptane) to give 6.55 g (69%) of the. title compound as light brown crystals. 1H NMR (300MHz; CDCI3): 8 3.38 (brs, 3H), 6.88 (d, 2H), 7.22-7,46 (m, 5H), 7.62 (d, 2H); HPLC-MS : mlz = 354.0 (M+1); Rt = 4.54. min.
Example 523 (General procedure 20)
Methyl-phenyl-carbamic acid 4,-trifluoromethyl-biphenyl-4-yI ester
The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-trifluoromethylphenyIboronic acid. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1:9) (42%, light brown crystals). HPLC-MS : mlz = 372.1 (M+1); Rt = 5.19 min.
Example 524 (General procedure 20)
Methyl-phenyl-carbamic acid 4,-trifluoromethoxy-biphenyI-4-yi ester
The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-trifIuoromethoxyphenylboronic acid. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1:9) (17%, brown oil). HPLC-MS : m/z= 388.1 (M+1); Rt= 5.27 min.
Example 525 (General procedure 20)
Methyl-phenyl-carbamic acid 4-pyridin-3-yl-phenyl ester
The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and pyridine-3-boronic acid. The crude product was purified by preparative HPLC (Gilson) (5%, brown oil).
1H NMR (300MHz; CDCI3): 8 3.46 (br s, 3H), 7.29-7.46 (m, 7H), 7.61 (d, 2H), 7.88 (dd, 1H), 8.41 (d, 1H), 8.78 (d, 1H); HPLC-MS : mlz = 305.1 (M+1); Rt = 2.99 min.
Example 526 (General procedure 20)
Methyl-phenyl-carbamic acid 4-(5-chloro-thiophen-2-yI)-phenyl ester
The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 5-chloro-2-thiopheneboronic acid. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1:9) (53%, pink crystals).

1H NMR (300MHz; CDCI3): 5 3.43 (br s, 3H), 6.87 /d, 1H), 7.00 (d, 1H), 7.13 (br d, 2H), 7.26-7.48 (m, 7H); HPLC-MS: mlz = 344.0 (M+1); Rt = 5.16 min.
Example 527 (General procedure 20)
Methyl-phenyl-carbamic acid 4,-benzylsuIfarnoyI-biphenyi-4-yl ester
The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-benzyIsulfamoyIbenzeneboronic acid. The crude product was purified by preparative HPLC (Gilson) (35%, pink crystals). HPLC-MS : m!z = 473.0 (M+1); Rt = 4.80 min. ■
Example 528
Methyl-phenyl-carbamic acid 4-styryl-phenyl ester
Styrene (1.2 mmol), N-methyldicyclohexyiamine (1.2 mmol), Pd2(dba)3 (0.03 mmol), Pd(P(f-Bu)3)2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 17% yield as colorless crystals. HPLOMS : mfz = 330.1 (M+1); Rt= 5.08 min.
Example 529
Methyl-phenyl-carbamic acid 4-phenyIethynyl-phenyI ester
Phenylacetylene (1.2 mmol), diisopropylarnine (1.2 mmol), Cul (0.03 mmol), Pd2(dba)3 (0.03 mmol), Pd(P(M3u)3>2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 41% yield as brown oil. HPLC-MS : mlz= 328.1 (M+1); Rt = 5.07 min..
Example 530
3-[4-(Methyl-phenyl-carbamoyloxy)-phenyri-acrylic acid methyl ester

Methylacrylate (1.2 mmol), N-methyldicyclohexylamine (1.2 mmol), Pd2(dba)3 (0.03 mmol), Pd(P(f-Bu)3)2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen.. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred
at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 70% yield as a yellow solid. HPLC-MS : m/z= 312.1 (M+1); Rt = 4.19 min.
Example 531 (General procedure 8)
Methyl-phenyl-carbamic acid 5-phenyIsuIfanyl-pyrazoI-1-yI ester
The title compound was prepared from 1-hydroxy-5-phenyIsulfanylpyrazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (80%, oil).
1H NMR (300MHz; CDC!3): S 3.36 (br s, 3H), 6.47 (d, 1H) 7.16-7.32 (m, 10H), 7.40 (df 1H); HPLC-MS : mlz = 326.0 (M+1); Rt = 4.42 min.
Example 532 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(toIuene-4-sulfonylamino)-phenyI ester
The title compound was prepared in 8% yield as a clear oil using toluenesulfonyl chloride as
the aryl sulfonyl chloride.
HPLC-MS : mtz = 397.1 (M+1); R{ = 4.13 min
Example 533 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(5-pyridin-2-yl-thiophene-2-sulfonylamino)-phenyl ester
The title compound was prepared in 7% yield as an oil using 5-pyridin-2-yl-thiophene-2-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z= 466.1 (M+1); Rt = 4.23 min.
Example 534 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(1-methyHH-imidazole-4-sulfonylamino)-phenyl ester
The title compound was prepared in 21% yield as crystals using 1-methyMH-imidazole-4-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS :m/z= 387.1 (M+1); Rt= 3.14 min.
Example 535 (General procedure 21)
tfethyl-phenyl-carbamic acid 4-(2f5-dichlorothiophene-3-suIfonylamino)-phenyI ester
The title compound was prepared in 2% yield as an oil using 2,5-dichloro-thiophene-3-sulfonyl chloride as the aryl sulfonyl chloride. rIPLC-MS : m/z = 458.6 (M+1); Rt = 4.38 min.
Example 536 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(5-chloro-1,3-dimethyl-1 H-pyrazo!e-4-sulfonylamino)-phenyI
ester
The title compound was prepared in 3% yield as an oil using 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z = 435.1 (M+1); Rt = 3.74 min.
Example 537 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(5-dimethylamlno-naphthalene-1-sulfonylamino)-phenyl ester
The title compound was prepared in 14% yield as orange crystals using 5-dimethyIamino-naphthalene-1 -sulfonyl chloride as the aryl sulfonyl chloride. HPLC-MS : m/z = 476.0 (M+1); Rt = 4.48 min.
Example 538 (General procedure 21)
2-[4-(Methyl-phenyl-carbamoyIoxy)-phenyisuIfamoyl]-benzoic acid methyl ester
The title compound was prepared in 48% yield as a yellow oil using 2-chlorosulfonyl-benzoic acid methyl ester as the aryl sulfonyl chloride. HPLC-MS : m/z = 441.1 (M+1); R{ = 4.19 min.
Example 539 (General procedure 21)
Methyl-phenyl-carbamic acid 4-(3I4-difluoro-benzenesulfonylamino)-phenyl ester
The title compound was prepared in 1% yield as a clear oil using 3,4-difluoro-benzenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS : mlz = 419.1 (M+1); Rt = 4.23 mln.
Example 540 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-pyridin-2-ylmethyl-phenyI ester
4-Pyridin-2-yImethyI-pheno! was prepared following general procedure PVe3 using pyridine-2-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (86%, oil).
1H NMR (400MHz; CDCI3): 8 3.40 (br s, 3H), 4.14 (s, 2H), 7.04-7.12 (m, 4H), 7.21-7.26 (m, 3H)f 7.32-7.40 (m, 4H), 7.55 (t, 1H), 8.52 (df 1H).
Example 541 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-pyridin-3-yimethyl-phenyl ester
4-Pyridin-3-ylmethyl-phenol was prepared following general procedure PVe3 using pyridine-3-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (50%, oil).
1H NMR (400MHz; CDCI3): 5 3.42 (brs, 3H), 3.96 (s, 2H). 7.03-7.42 (m, 11H), 8.46 (d, 1H), 8.49 (dp 1H).
Example 542 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-(4-trifIuoromethyI-benzyI)-phenyl ester
4-(4-TrifIuoromethyl-benzyl)-phenol was prepared following general procedure PVe3 using 4-trifluoromethylbenzaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (92%, oil).
1H NMR (400MHz; CDCI3): S 3.42 (br s, 3H)( 4.00 (s, 2H)f 7.06 (br s, 2H), 7.13 (d, 2H), 7.24-7.40 (m, 7H), 7.52 (d, 2H).
Example 543 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-thiophen-3-ylmethyl-phenyl ester
4-Thiophen-3-ylmethyl-phenol was prepared following general procedure PVe3 using thio-

phene-3-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (83%, oil). 1H NMR (400MHz; CDC!3): S 3.42 (bs, 3H), 3.95 (s, 2H), 6.86-7.39 (m, 12H).
Example 544 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-thiophen-2-ylmethyl-phenyl ester
4-Thiophen-2-ylmethyl-phenol phenol was prepared following general procedure PVe3 using thiophene-3-carboxaidehyde. Subsequent carbamoylation using genera! procedure 1 (CH2C!2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (83%, oil).
1H NMR (400MHz; CDC!3): S 3.40 (br s, 3H), 4.13 (s, 2H), 6.78 (dd, 1H), 6.90. (dd, 1H), 7.04 (brd, 2H), 7.13 (dd, 1H), 7.20-7.39 (m, 7H). HPLC-MS : m/z- 324.1 (M+1); Rt = 4.82 min.
Example 545
4-Hydroxy-piperidine-1-carboxyIic acid 4-[2-(toIuene-4-suIfonyIamino)-ethyI]-pheny] ester
N-Boc protected tyramin (10 mmol), triethylamine (10 mmol) and 3-[4-(tert-Butyl-dimethyl-silanyloxy)-piperidine-1-carbonyI]-1-methyI-3H-imidazoI-1-ium; iodide (10 mmol) in MeCN (25 mL) was stirred at room temperature for 16 hours. Acetonitrile was removed by evaporation and the crude product was purified by flash chromatography (Quad flash 40, EtOAc-heptane 1:2) providing 72% 4-tert-butyIsilanyloxy-piperidine-1-carboxyIic acid 4-(2-tert-butoxycarbony!amino-ethyI)-phenyl ester. This was deprotected by stirring with a 3.2 M solution of HCI in Et20 (50 mL) for 3 h at rt and subsequently washed with ether to give 91% of 4-(4-hydroxy-piperidine-1-carbonyloxy)-phenyI-ammonium; chloride as a solid. This compound was N-tosyiated as described for methyl-phenyl-carbamic acid 4-[2-(toluene-4-sulfonylamino)-ethy[]-phenyl ester to give the title compound in 26% yield as yellow crystals after purification by flash chromatography (Quad flash 12, ChfeCtrMeOH 95:5). HPLC-MS : mfc= 391.0 (M+1); Rt= 3.04 min.
Example 546
4-Hydroxy-piperidine-1 -carboxylic acid 4-[2-(5-pyridin-2-yI-thiophene-2-sulfonylamino)-ethyI]-phenyi
4-(4-Hydroxy-piperidine-1-carbonyIoxy)-phenyl»ammonium; chloride (see above) was N-

sulfonylated as described for methyl-phenyl-carbamic acid 4-[2-(5-pyridin-2-yl-thiophene-2-sutfonylamino)-ethyO-phenyl ester to give the title compound in 59% yield as an oil after purification by preparative HPLC (Gilson). HPLC-MS : m/z = 488.0 (M+1); Rt = 3.10 min.
Example 547
4-Hydroxy-piperidine-1 -carboxylic acid 4-(5-pyridin-2-yl-thiophene-2-sulfonyiamino)-phenyl ester
N-Boc protected 4-aminophenol (10 mmol), triethylamine (10 mmol) and 3-[4-(tert-ButyI-dimethyl-siIanyloxy)-piperidine-1-carbonyI]-1«methyl-3H-imida2ol-1-ium; iodide (10 mmol) in MeCN (25 mL) was stirred at room temperature for 16 hours. Acetonitrile was removed by evaporation and the crude product was purified by flash chromatography (Quad flash 40, EtOAc-heptane 1:2) providing 64% 4-tert-butyisilanyioxy-piperidine-1-carboxylic acid 4-tert-butoxycarbonylamino-phenyl ester. This was deprotected by stirring with a 3.2 M solution of HCI in Et20 (50 mL) for 3 h at rt and subsequently washed with ether to give 91 % of 4-(4-Hydroxy-piperidine-1-carbonyloxy)-phenyl-ammoniurn; chloride as a hygroscopic solid. This compound was N-sulfonylated as described for methyl-phenyl-carbamic acid 4-[2-(5-pyridin-2-yl-thiophene-2-sulfonylamino)-ethy!]-phenyI ester to give the title compound in 1% yield as crystals after purification by preparative HPLC (Gilson). HPLC-MS :/77/z= 482.8 (M+1); Rt = 1.01 min.
Example 548
Methyl-phenyl-carbamic acid 4-[2-(4-amino-benzenesulfonylamino)-ethyI]-phenyl ester
Methyl-phenyl-carbamic acid 4-[2-(4-nitro-benzenesulfonylamino)-ethy(]-phenyl ester, 5% palladium on carbon, and ethanol were stirred under hydrogen at 1 bar and rt for 16 h. Filtration and removal of ethanol produced the title compound in 94% yield as an oil. HPLC-MS: mlz = 426.1 (M+1); Rt= 3.61 min.
Example 549
Methyl-phenyl-carbamic acid 4-{2-[(pyridine-3-carbonyl)-amino]-ethyI}-phenyl ester
A solution of 3-pyridinecarboxylic acid (0.3 mmol), EDAC (0.36 mmol) and triethylamine (0.36 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazofe and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyl)phenyl ester as its TFA salt (0.3 mmol). The mixture was stir-

stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 15%
yield as an oil.
HPLC-MS: m/z= 376.1 (M+1); Rt = 3.01 min.
Example 550
Methyl-phenyl-carbamic acid 4-[2-(2-dimethylamino-acetyIamino)-ethyI]-phenyl ester
A solution of N.N-dimethyiglycine, HCI (0.3 mmol), EDAC (0.36 mmol) and triethylamine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyI)phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 66% yield as an oil. HPLC-MS : mlz = 356.4 (M+1); Rt = 2.09 min.
Example 551 (General procedure 23)
Methyl-phenyl-carbamic acid 2-(toluene-4-sulfony!)-1,2,3,4-tetrahydro-isoquinolin-7-yl ester
The title compound was prepared using methyl-phenyl-carbamic acid 4-[2-(toluene-4-suifonylamino)-ethyI]-phenyl ester as the sulfonamide. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 2:3) (71%, yellow oii). HPLC-MS : m/z= 437.4 (M+1); Rt = 4.43 min.
Example 552
Methyl-phenyl-carbamic acid 4-[4-(2-pyrroIidin-1-yl-ethoxy)-benzyI]-phenyI ester
To a stirred solution of 1-[2-(4-bromo-phenoxy)-ethy!]-pyrrolidine (2.89 g, 10.7 mmol) in THF (30 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (7 mL, 10.2 mmol) over a 5-min period at -78°C. The mixture was stirred at -78°C for 15 min before 4-trimethylsilyloxybenzaldehyde (2.08 g, 10.7 mmol) was added. The mixture was allowed to warm to rt during 20 min and quenched with water. Extraction with CH2CI2, drying (MgS04), filtration and evaporation provided the crude diarylmethanol which was dissolved in CH2Ci2 (30 mL) and stirred with triethylsilane (4 mL) and TFA (5 mL) for 16 h at rt. Evaporation gave 3.0 g (84%) 4-[4-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenol. This was carbamoylated using general procedure. 1 (CH2CI2 was used as solvent) to give the title product after purification by preparative HPLC (Gilson) (35%, oil). HPLC-MS : m/z = 431.5 (M+1); Rt = 2.93 min.

Example 553 (General procedure 24) 4-Hydroxy-piperidine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
The title compound was prepared as its hydrochloride using 4-pyridin-2-yimethy!-phenol as the phenol.
1H NMR (300MHz; D20): S 1.50 (br s, 2H), 1.90 (df 2H), 3.04-3.27 (m, 2H), 3.78-4.08 (m, 3H), 4.41 (s, 2H), 7.07 (d, 2H), 7.30 (df 2H), 7.79-7.85 (m, 2H), 8.40 (dt, 1H), 8.55 (d, 1H).
Example 554 (Genera! procedure 24) 4-Hydroxy-piperidine-1-carboxyIic acid 4-pyridin-3-ylmethyI-phenyl ester
The title compound was prepared as its hydrochloride using 4-pyridin-3-yImethyl-phenol as the phenol.
1H NMR (300MHz; D20): 8 1.48 (br s, 2H), 1.90 (d, 2H), 3.03-3.26 (m, 2H), 3.80-4.05 (m, 3H), 4.18 (s, 2H), 7.03 (d, 2H), 7.25 (d, 2H), 7.40 (dd, 1H), 8.40 (d, 1H), 8.54-8.57 (m, 2H).
Example 555 (General procedure 24)
4-Hydroxy-piperidine-1-carboxylic acid 4-(4-trifluoromethyI-benzyI)-phenyi ester
The title compound was prepared using 4-(4-trifluoromethyl-benzyl)-phenol as the phenol. 1H NMR (300MHz; D20): 5 1.43-1.55 (m, 2H), 1.76-1.88 (m, 2H), 3.10-3.29 (m, 2H), 3.79-3.94 (m, 5H), 6.97 (d, 2H), 7.08 (d. 2H), 7.20 (d, 1H), 7.45 (d, 2H).
Example 556 (General procedure 23)
Methyl-phenyl-carbamic acid 2»[4-(2-pyrroIidin-1-yl-ethoxy)-benzenesulfonyl]-1,2,3,4-
tetrahydro-isoquinolin-7-yI ester
The title compound was prepared using methyl-phenyl-carbamic acid 4-{2-[4-(2-pyrrolidin-1-yI-ethoxy)-benzenesulfonylamino]-ethyI}-phenyl ester as the sulfonamide. The crude product was purified by preparative HPLC (Gilson) and isolated as its TFA salt (45%, foam). HPLC-MS : m/z= 536.2 (M+1); Rt = 3.10 min.
Example 557
Methyl-phenyl-carbamic acid 4-{2-[(1-methyI-piperidine-4-carbonyl)-amino]-ethyI}-phenyl ester

A solution of 1-methylpiperidine-4-carboxylic acid (0.3 mmol), EDAC (0.36 mmol) and triethy-lamine (1.0 mrnol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyI)phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 5% yield as an oil. HPLC-MS : m/z= 396.4 (M+1); Rt = 2.03 min.
Example 558 (General procedure 23)
Methyl-phenyl-carbamic acid 2-(3,4-difluoro-benzenesuIfonyl)-1,2,3,4-tetrahydro-isoquinoIin-
7-yI ester
The title compound was prepared using methyl-phenyl-carbamic acid 4-[2-(3,4-difluoro-benzenesu!fonylamino)-ethyI]-phenyl ester as the sulfonamide. The crude product was purified by preparative HPLC (Gilson) (24%, oil). HPLC-MS : m/z= 481.0 (M+23); Rt= 4.73 min.
Example 559 (General procedure 23)
Methyl-phenyl-carbamic acid 1-methyl-2-(toluene-4-sulfony!)-1 ^^^-tetrahydro-isoquinoIin-T-
yl ester
The title compound was prepared using methyl-phenyl-carbamic acid 4-[2-(toluene-4-sulfonylamino)-ethyI]-phenyl ester as the sulfonamide and acetaldehyde in stead of formaldehyde. The crude product was purified by preparative HPLC (Gilson) (22%, brown oil). HPLC-MS : m/z = 451.5 (M+1); Rt = 4.43 min.
Example 560 (General procedure 23)
Methyl-phenyl-carbamic acid 2-[4-(4-methyl-piperazin-1-yl)-benzenesuIfonyl]-1,2,3,4-
tetrahydro-isoquinolin
The title compound was prepared using methyl-phenyl-carbamic acid 4-{2-[4-(4-methyl-piperazin-1-yl)-benzenesulfonylamino]-ethy(}-phenyi ester as the sulfonamide. The crude product was purified by preparative HPLC (Gilson) and isolated as its TFA salt (79%, crystals). HPLOMS : m/z= 521.5 (M+1); Rt= 2.65 min.

Example 561 (General procedure 23)
Methyl-phenyl-carbamic acid 1 -methyl-2-[4-(4-methyl-piperazin-1 -yl)-benzenesulfonyl]-
1,2,3,4-tetrahydro-isoquinoIin-7-yl ester
The title compound was prepared using methyl-phenyl-carbamic acid 4-{2-[4-(4-methyl-piperazin-1-yI)-benzenesulfonyIamino]-ethyl}-phenyl ester as the sulfonamide and acetalde-hyde in stead of formaldehyde. The crude product was purified by preparative HPLC (Gilson) (12%, brown oil). HPLC-MS: mtz* 535.4 (M+1); Rt= 2.69 min.
Example 562
3,3-Dimethyl-4-{2-[4-(methyl-pheny!-carbamoy^
A solution of 3,3-dimethylglutaric anhydride (0.3 mmol), diisopropylethylamine (0.30 mmol) and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyI)phenyl ester as its TFA salt (0.3 mmol) in CH2CI2 (3 mL) was stirred 1 h at rt. The mixture was washed with water and brine, dried and evaporated to give the title compound in 95% yield as an oil. HPLC-MS : m/z = 413.2 (M+1); Rt = 3.20 min.
Example 563
Methyl-phenyl-carbamic acid 4-{2-[4-(4-methyl-piperazin-1 -yl)-benzoylamino]-ethyI}-phenyl ester
A solution of 4-(4-methylpiperazino)benzoic acid (0.3 mmol), EDAC (0.36 mmol) and triethyl-amine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazo!e and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyI)phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 54% yield as its crystalline hydrochloride after treatment with HCI in diethyl ether. HPLC-MS : mlz = 473.2 (M+1); Rt = 2.22 min.
Example 564
Methyl-phenyl-carbamic acid 4-{2-[4-(4-methyI-piperazin-1 -ylmethy[)-benzoyiamino]-ethyl}-pheny! ester
A solution of 4-(4-methylpiperazinyI)methyl benzoic acid (0.3 mmol), EDAC (0.36 mmol) and triethylamine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-

methyl-N-phenyl-carbamic acid 4-(2-amino-ethyl)phenyI ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 25% yield as its crystalline hydrochloride after treatment with HCI in diethyl ether.. HPLC-MS : mfz= 487.3 (M+1); Rt = 2.13 min.
Example 565
Methyl-phenyl-carbamic acid 4-[2-(4,4-dimethyI-2,6-dioxo-piperidin-1-yI)-ethyl]-phenyI ester
A solution of 3,3-dimethylglutaric anhydride (0.3 mmol), diisopropylethylamine (0.30 mmol) and N-methyl-N-phenyl-carbamic acid 4-(2-amino-ethyl)phenyI ester as its TFA salt (0.3 mmol) in CH2CI2 (3 mL) was stirred 1 h at rt. Thionylchloride (3 mmol) was added and the mixture was stirred for 2 h at rt. Addition of ethanol (5 mL) followed by evaporation to dryness gave a crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1:1). This gave the title compound in 23% yield as crystals. Furthermore 3,3-dimethyI-4-{2-[4-(methyl-phenyl-carbamoyloxy)-pheny[]-ethylcarbamoyl}-butyricacid ethyl ester could be isolated in 27% yield as an oil (see characterization below) 1H NMR (400MHz; CDCI3): 5 1.04 (s, 6H), 2.47 (s, 4H), 2.79 (t, 2H), 3.42 (br s, 3H), 3.97 (t, 2H), 7.03 (br d, 2H), 7.21-7.28 (m, 3H), 7.33-7.41 (m, 4H). HPLC-MS : m/z = 395.2 (M+1); Rt = 4.23 min.
Example 566
3,3-DimethyI-4-{2-[4-(methyl-phenyl-carbamoyIoxy)-phenyI]-ethylcarbamoyI}-butyricacid ethyl ester
For experimental details, see preparation of methyl-phenyl-carbamic acid 4-[2-(4,4-dimethyl-
2,6-dioxo-piperidin-1 -yl)-ethyl]-phenyl ester.
1H NMR (400MHz; CDCl3): 8 1.05 (s, 6H), 1.24 (t, 3H), 2.19 (s, 2H), 2.22 (s, 2H), 2.80 (t,
2H), 3.42 (br s, 3H), 3.50 (q, 2H), 4.1 (q, 2H), 6.53 (t, 1H), 7.03 (br d, 2H), 7.18 (d, 2H), 7.26
(t,1H)( 7.33-7.41 (m,4H),
HPLC-MS: m/z = 441.2 (M+1); Rt = 4.11 min.
Example 567
Methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester
To a solution of 4-hydroxymethylphenol (10 mmol) and 4-diazabicyclo[2.2.2]octane (DABCO) (10 mmol) in CH2CI2 (30 mL) was added N-methyl-N-phenylcarbamoyI chloride (10 mmol).

The reaction mixture was stirred for 16 hours at rt, added CH2Cl2 (20. mL) and washed with 1M aqueous HCI and brine. The organic phase was dried (MgS04).and evaporated to give the crude product which was purified by FC (Quad flash 40 EtOAc-Heptane 1:1) to give 2-18 g (85%) of the title compound as an oil.
1H NMR (400MHz; CDCI3): S. 1.70 (br s, 1H), 3.40 (br s, 3H), 4.66 (s, 2H), 7.08 (br d, 2H), 7.25-7.42 (m, 7H); HPLC-MS : mlz = 258.1 (M+1); Rt = 2.99 min.
Example 568
Methyl-phenyl-carbamic acid 4-(2-hydroxy-ethy[)-phenyl ester
To a solution of 4-(2-Hydroxyethyl)phenol (10 mmol) and 4-diazabicyclo[2.2.2]octane (DABCO) (10 mmol) in CH2CI2 (30 mL) was added N-methy!-N-pheny)carbamoy! chloride (10 mmol). The reaction mixture was stirred for 16. hours at rt, added CH2Cl2 (20 mL), and washed with 1M aqueous HCI and brine. The organic phase was dried (MgS04) and evaporated to give the 2.69 g (99%) of the title compound as crystals.
1H NMR (400MHz; CDCI3): 8 1.52 (br s, 1H), 2.54 (t, 2H), 3.41 (br s, 3H), 3.81 (t, 2H), 7.04 (br d, 2H), 7.20 (d, 2H), 7.22-7.42 (m, 5H); HPLC-MS : m/z= 272.1 (M+1); Rt = 3.17 min.
Example 569 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(4-dimethylamino-pyridin-2-ylmethyi)-phenyl ester
A solution of 2-(dimethyIamino)ethanoI (32 mmol) in hexane (120 mL) was cooled to - 5°C and n-BuLi (64 mmol) was added. After 30 min 4-(dimethyIamine=pyridine (16 mmol) was added and the red-orange mixture was stirred for further 1 h. The solution was cooled to -78 °C and 4-(trimethylsilyIoxy)benzaldehyde (40 mmol) dissolved in hexane (80 mL) was added and the suspention was allowed to warm to rt over 20 min. The reaction mixture was quenched with water, and the aqueous phase was washed with CH2CI2, The aqueous phase was. evaporated to dryness, added Nal (96 mmol) and dissolved in MeCN (160 mL). Addition of trimethylsilylchloride (96 mmol) and stirring at rt for 16h. The purple reaction mixture was evaporated to dryness and treated with an aqueous solution of Na2S03 and pH was adjusted to 8. Extraction with CH2CI2 gave after evaporation 560 mg (15%) slightly impure 4-(4-dimethylaminO"pyridin-2-ylmethyl)phenol as yellow crystals. This was carbamoylated using general procedure 1 (CH2CI2 was used as solvent) to give the title, product as its hydrochloride after purification by preparative HPLC (Gilson) and treatment with HCI in Et20 (48%, ligt yellow crystals).

HPLC-MS: mlz = 362.2 (M+1); Rt = 2.27 min.
Example 570 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(4-imidazol-1-yl-phenoxymethy!)-phenyl ester
The title compound was prepared in 53% yield as light yellow crystals using and 4-imidazol-1-yt-phenol. 1H NMR (400MHz; CDC)3): 8 3.42 (br s, 3H), 5.08 (s, 2H), 7.03 (d, 2H), 7.12-7.42 (m, 15H), 7.77 (s, 1H); HPLC-MS : mlz = 400.1 (M+1); Rt = 2.62 min.
Example 571 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[4-(2-dimethylamino-ethyl)-phenoxymethy[]-phenyl ester
The title compound was prepared in 52% yield as colorless crystals using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 4-(2-dimethylaminoethyI)-phenol. 1H NMR (400MHz; CDCi3): 5 2.85 (s, 6H), 2.98-3.02 (m, 2H), 3.17-3.21 (mf 2H), 3.42 (br s, 3H), 5.02 (s, 2H), 6.90 (d, 2H), 7.12 (d, 2H), 7.25-7.43 (m, 7H); HPLC-MS : m/z = 405.2 (M+1); Rt = 2.91 min.
Example 572 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(pyrazoI-1-yloxymethy!)-phenyl ester
The title compound was prepared in 79% yield as an oil using and 1-hydroxypyrazoIe. 1H NMR (400MHz; CDCl3): 5 3.42 (br s, 3H), 5.26 (s, 2H), 6.03 (t, 1H), 6.95 (dd, 1H), 7.11 (br s, 2H), 7.25-7.42(m, 8H); HPLC-MS : m/z= 324.1 (M+1); Rt= 3.58 min.
Example 573 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(imidazo!-1-yloxymethyI)-phenyl ester
The. title compound was prepared as its TFAsalt in 87% yield as a solid using methyl-phenyl-carbamic acid 4-hydraxymethyl-phenyl ester and 1-hydroxyimidazole, hydrochloride. 1H NMR (400MHz; CDCI3): S 3.42 (br s, 3H)f 5.21 (s, 2H), 6.95 (s, 1H), 7.16-7.45 (m, 10H), 8.28 (br s, 1H); HPLC-MS :m/z= 324.1 (M+1); Rt = 1.92min.
Example 574 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(2-oxo-2H-pyridin-1-ylmethy!)-phenyl ester

The title compound was prepared in 29% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyridine. in addition 50% of the isomeric methyl-phenyl-carbamic acid 4-[2-(pyridin-2-yIoxy)-ethyO-phenyl ester was isolated, see characterization below. 1H NMR (400MHz; CDCI3): £.3.05 (t, 2H)f 3.41. (br s, 3H), 4.14 (s, 2H)f 6.08. (t, 1H)f 6.66 (d, 1H), 6.90 (dd, 1H), 7.02 (br s, 2H), 7.10 (d, 2H), 7.25-7.42 (m, 6H); HPLC-MS : mlz = 349.2 (M+1); Rt = 3.04 min.
Example 575 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
The title compound was prepared in 50%. yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyridine. In addition 29% of the isomeric methyl-phenyl-carbamic acid 4-(2-oxo-2H-pyridin-1-ylmethyi)-phenyl ester was isolated, see characterization above. 1H NMR (400MHz; CDCI3): 5 3.08 (t, 2H), 3.41 (br s, 3H), 4.49 (s, 2H), 6.73 (d, 1H), 6.88 (dd, 1H), 7.05 (br d, 2H), 7.22-7.42 (m, 7H), 7.61 (dt, 1H), 8.18 (dd, 1H); HPLC-MS : mlz = 349.2 (M+1); Rt = 3.97 min.
Example 576 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[2-(4-imidazoM-yl-phenoxy)-ethyl]-phenyl ester
The title compound was prepared as its TFA salt in 62% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 4-imidazol-1-yl-phenol. 1H NMR (400MHz; CDCI3): 5 3.11 (t, 2H)f 3.42 (br s, 3H), 4.22 (s, 2H)f 7.00-7.10 (m, 5H)f 7.25-7.42 (m, 9H), 7.52 (s, 1H)f 8.81 (s, 1H); HPLC-MS : mlz = 414.2 (M+1); Rt = 2.73 min.
Example 577 (General procedure 25)
Methyl-phenyl-carbamic acid 4-{2-[4-(2-dimethylamino-ethyl)-phenoxy]-ethyl}-phenyl ester
The title compound was prepared as its TFA salt in 92% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 4-(2-dimethyIaminoethyl)-phenoL HPLC-MS : mlz = 419.2 (M+1); Rt = 2.77 min.
Example 578 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[2-(pyrazoM-yloxy)-ethyl]-pheny! ester
The title compound was prepared in 62% yield as an oil using methyl-phenyl-carbamic acid

4-(2-hydroxy-ethyl)-phenyl ester and 1-hydroxypyrazoIe.
1H NMR (400MHz; CDCl3): 8 3.02 (t( 2H)( 3.42 (br s, 3H), 4.50 (t, 2H), 6.16 (t, 1H), 7.05 (br
d, 2H), 7.20-7.41 (m, 9H); HPLC-MS : mlz= 338.2 (M+1); Rt = 3.74 min.
Example 579 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[2-(imidazoI-1-yioxy)-ethyl]-phenyI ester
The title compound was prepared as its TFA salt in 79% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyI ester and 1-hydroxyimidazoIe hydrochlorid. 1H NMR (400MHz; CDCI3): 8 3.06 (t, 2H), 3.42 (br s, 3H), 4.52 (t, 2H), 7.08-7.42 (m, 11H), 8.53 (s, 1H); HPLC-MS : m/z = 338.2 (M+1); Rt= 2.18 min.
Example 580 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(5-methyI-pyridin-2-ylmethyI)-phenyI ester
To a stirred solution of 2-bromo-5-methylpyridine (3.45 g, 20 mmol) in THF (10 ml_) was added dropwise 1.6 M solution in hexanes n-BuLi (12 mL, 19.2 mmol) over a 10-min period at -78°C. The mixture was stirred at -78°C for 2 min before 4-trimethylsilyloxybenzaldehyde (4.2 g, 21.6 mmol) dissolved in THF (10 mL) was added. The mixture was allowed to warm to • -40 °C and quenched with water. The pH of the aqueous phase was adjusted to 7 which causes precipitation of 4-[hydroxy-(5-methyI-pyridin-2-yI)~methyI]phenoL This was isolated by filtration to give 1.13 g (27%) of 4-[hydroxy-(5-methyl-pyridin-2-yl)-methyl]phenol as crystals. This intermediate was dissolved in CH2CI2 (15 mL) and stirred with triethylsiiane (4 mL) and TFA (5 mL) for 16. h at 50 °C. Evaporation gave 99% of 4-(5-methyl-pyridin-2-ylmethyl)phenol as a hygroscopic solid. This was carbamoylated using general procedure 1 (CH2Cl2 was used as solvent and N-phenyl-N-methyl carbamoyl chlorid) to give 99% of the title product as its crystalline hydrochloride after purification by flash chromatography (Quad flash 12, EtOAc-heptane) and treatment with HCI in Et20.
1H NMR (400MHz; CDCI3): 8 2.50 (s, 3H), 3.41 (br s, 3H), 4.57 (s, 2H), 7.10 (br s, 2H), 7.25-7.42 (m, 8H), 8.00 (dd, 1H), 8.46 (br s, 1H); HPLC-MS: mlz = 333.1 (M+1); Rt = 2.60 min.
Example 581 (General procedure 24)
4-Hydroxy-piperidine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyI ester
The title compound was prepared as its hydrochloride using of 4-(5-methyl-pyridin-2-

flmethyI)phenol as the phenol.
H NMR (300MHz;. CDCl3): S 1.57-1.67 (m, 3H), 1.95 (d, 2H), 2.51 (s, 3H), 3.21-3.40 (m, 2H), 3.90-4.05 (m, 3H), 4.58 (s, 2H), 7.11 (d, 2H), 7.38 (d, 2H), 7.45 (d, 1H), 8.02 (d, 1H), 3.48(brs, 1H).
Example 582 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(4-oxo-4H-pyridin«1-ylmethyl)-phenyl ester
The title compound was prepared in 33% yield as colorless crystals using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 4-hydroxypyridine. 1H NMR (400MHz; CDCI3): S 3.43 (br s, 3H), 4.92 (sf 2H), 6.43 (d, 2H), 7.17 (br s, 4H), 7.22-7.42 (m, 9H); HPLC-MS : mlz = 335.0 (M+1); Rt = 2.55 min.
Example 583 (General procedure 25)
Methyl-phenyl-carbamic acid 4-[2-(pyridin-3-yloxy)-ethyi]-phenyl ester
The title compound slightly contaminated with tributylphosphine oxide was prepared in 80%
yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyl ester and 3-
hydroxypyridine.
1H NMR (400MHz; CDCI3): 5 3.11 (t, 2H), 3.42 (br s, 3H), 4.23 (t, 2H), 7.07 (br d, 2H), 7.24-
7.41 (m, 9H)( 8.29 (br s, 1H), 8.40 (br s, 1H); HPLC-MS : mlz = 349.2 (M+1); Rt = 2.87 min.
Example 584 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester
The title compound was prepared in 66% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 2-hydroxypyridine. 1H NMR (400MHz; CDCI3): 5 3.42 (br sf 3H), 5.12 (s, 2H), 6.13 (t, 1H), 6.60 (d, 1H), 7.10 (br s, 2H), 7.22-7.41 (m, 9H); HPLC-MS : mlz = 335.2 (M+1); Rt = 2.97 min.
Example 585 (General procedure 25)
Methyl-phenyl-carbamic acid 4-(pyridin-3-yloxymethyl)-phenyl ester
The title compound was prepared in 43% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 3-hydroxypyridine. 1H NMR (400MHz; CDCI3): S 3.44 (br

s, 3H), 5.12 (s, 2H), 7.17 (br s, 2H), 7.27-7.46 (m, 9H), 8.29 (br s, 1H), 8.49 (br s, 1H); HPLC-MS : m/z = 335.0 (M+1); Rt = 2.74 min.
Example 586 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(2,5-dioxo-pyrroIidin-1-yI)-ethyI]-phenyl ester
The title compound was prepared in 85% yield as crystals using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyI ester and succinimide. 1H NMR (400MHz; CDCl3): 5 2.65 (s, 4H), 2.86 (t, 2H), 3.41 (br s, 3H), 3.72 (t, 2H), 7.04 (br d, 2H), 7.19 (d, 2H), 7.26-7.42 (m, 5H); HPLC-MS : m/z = 353.2 (M+1); Rt = 3.17 min.
Example 587 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(1,3-dioxo-1,3-dihydro-pyrrolo[3,4-]pyridin-2-y[)-ethyI]-
phenyl ester
The title compound was prepared in 58% yield as crystals using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyl ester and 3,4-pyridinedicarboximide. 1H NMR (400MHz; CDCl3): 8 . 2.98 (tf 2H), 3.40 (br s, 3H), 3.93 (t, 2H), 7.05 (br d, 2H), 7.20-7.42 (m, 7H), 7.73 (dd, 1H), 9.06 (d, 1H), 9.12 (d, 1H); HPLC-MS : m/z = 402.1 (M+1); Rt = 3.56 min.
Example 588 (General procedure 26)
Methyl-phenyl-carbamic acid 4-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)-phenyl ester.
The title compound was prepared as its TFA salt in 22% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 2-mercapto-1-methyIimidazole. 1H NMR (400MHz; CDCI3): S 3.34 (s, 3H), 3.40 (br s, 3H), 4.30 (s, 2H), 6.98 (br s, 2H), 7.08-7.11 (m, 3H),7.27-7.42 (m, 5H), 7.48 (d, 1H); HPLC-MS : m/z = 354.1 (M+1); Rt = 2.12 min.
Example 589 (General procedure 26) Methyl-phenyl-carbamic acid 4-tetrazoM-ylmethyl-phenyl ester
The title compound was prepared in 6% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and tetrazole. 1H NMR (400MHz; CDCI3): S 3.42 (br s, 3H), 5.57 (s, 2H), 7.17 (br s, 2H), 7.26-7.42 (m, 7H), 8.52 (s, 1H); HPLC-MS : m/z = 332.0 (M+23); Rt = 3.24 min.

Example 590 (General procedure 26)
Methyl-phenyl-carbamic acid 4-(2,5-dioxo-pyrroIidin-1-yImethyI)-phenyl ester
The title compound was prepared in 57% yield as beige crystals using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and succinimide. 1H NMR (400MHz; CDCI3): S 2.68 (s, 4H), 3.41 (br s, 3H), 4.60. (s, 2H), 7.04 (br d, 2H), 7.23-7.41 (m, 7H); HPLC-MS : mlz = 339.1 (M+1); Rt= 3.40 min.
Example 590 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(2-thioxo-2H-pyridin-1-yl)-ethyl]-phenyl ester
The title compound was prepared in 25% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyl ester and 2-mercaptopyridine. HPLC-MS : mlz- 365.2 (M+1); Rt = 4.08 min.
Example 591 (General procedure 26)
Methyl-phenyl-carbamic acid 4-(1,3-dioxo-1,3-dihydro-pyrrolo[3,4)pyridin-2-ylmethyI)-phenyl
ester
The title compound was prepared in 21% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 3,4-pyridinedicarboximide. 1H NMR(400MHz; CDCI3); S 3.40 (brs. 3H)f 4.82 (s, 2H), 7.06 (d, 2H), 7.22-7.44 (m, 8H), 7.73 (d, 1H), 9.04 (df 1H), 9.12 (s, 1H); HPLC-MS : m/z= 388.0 (M+1); Rt = 3.80 min.
Example 592 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[1,2,4]1xiazol-1-ylmethyl-phenyl ester
The title compound was prepared as its TFA salt in 27% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 1,2,4-triazole. 1H NMR (400MHz; CDCI3): 5 3.42 (br s. 3H), 5.34 (s, 2H), 7.15 (br d, 2H), 7.26-7.43 (m, 7H), 8.10 (s. 1H), 8.38 (s, 1H); HPLC-MS : m/z= 309.1 (M+1); Rt = 2.74 min.
Example 593 (General procedure 26)
Methyl-phenyl-carbamic acid 4-(2-thioxo-2H-pyridin-1-ylmethyi)-phenyl ester

The title compound was prepared in 14% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 2-mercaptopyridine. HPLC-MS: mlz = 351.1 (M+1); Rt = 3.95 min.
Example 594 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(1-methyl-1H«imida2oI-2-ylsulfanyI)-ethyi]-phenyI ester
The title compound was prepared as its TFA salt in 37% yield as an oil using methyl-phenyi-carbarnic acid 4-(2-hydroxy-ethyI)-phenyI ester and 2-mercapto-1-methyIimidazole. NMR (400MHz; CDCl3): 8 3.01 (t, 2H), 3.40 (br s, 3H)f 3.47 (s, 1H), 3.64 (t, 2H), 6.92 (br d, 2H), 6.98 (s, 1H), 7.08 (d, 2H), 7.26-7.43 (m, 6H); HPLC-MS : mlz = 368.2 (M+1); Rt = 2.30 min.
Example 595 (General procedure 26)
Methyl-phenyl-carbamic acid 4-(2-tetrazol-1-yl-ethyl)-phenyl ester
The title compound was prepared in 10% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyI ester and tetrazole. NMR (400MHz; CDCI3): 8 3.19 (t, 2H), 3.40 (br s, 3H), 3.47 (s, 1H), 4.61 (t, 2H), 6.98-7.07 (m, 4H), 7.25-7.42 (m, 5H), 8.26 (s, 1H); i HPLC-MS : mlz = 324.1 (M+1); Rt = 3.36 min.
Example 596 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(pyrimidin-2-yloxy)-ethyI]-phenyI ester
The title compound was prepared in 24% yield as light yellow crystals using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyrimidine. NMR (400MHz; CDCI3): 8 3.11 (t, 2H), 3.42 (br s, 3H), 4.54 (tf 2H), 6.93 (t, 1H), 7.05 (d, 2H), 7.25-7.42 (m, 7H), 8.51 (d, 2H); HPLC-MS : mlz = 350.2 (M+1); Rt = 2.86 min.
Example 597 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(pyridin-4-ylsulfanyI)-ethyl]-phenyl ester
The title compound was prepared as its TFA salt in 5% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and 4-mercaptopyridine. NMR (400MHz; CDCI3): 8 3.07 (t, 2H), 3.36 (t, 2H), 3.44 (br s, 3H), 7.06 (br d, 2H), 7.20 (d( 2H), 7.25-7.43

(m, 7H)( 8.51 (d, 2H); HPLC-MS: mlz = 365.2 (M+1); Rt = 2.53 min.
Example 598 (General procedure 12)
4-(3-Amino-phenyI)-piperidine-1-carboxylic acid 4-(5-trifluoromethyI-pyridin2-yIoxy)-phenyl ester,
The title product was prepared from 4-(3-aminophenyI)piperidine (released form the correspondent hydrochloride by a standard procedure) and 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyI chloroformate, preparative HPLC (method C) (reaction performed in a mixture of dichloro-methane and dimethylformamide, 5:3). 1.7 M HCI in ethyl acetate was added to the pooled fractions containing the title product, and the fractions was evaporated to dryness (7%, light yellow solid). HPLC-MS m/z = (M+1) 458.0, Rt: 3.09 min.
Example 599 (Genera! procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(1-pyridin-3-yl-1H-imida2ol-2-ylsulfanyI)-ethy!]-phenyl ester
The title compound was prepared as its TFA salt in 5% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyI)-phenyl ester and 3-(2thio-1H-imidazoI-1-yl)pyridine. NMR (400MHz; CDCI3): 5 2.95 (t, 2H), 3.42 (br s, 2H), 3.56 (t, 3H), 6.98 (br d, 2H), 7.05 (d, 2H), 7.15 (d, 1H), 7.23-7.43 (m, 5H), 7.48 (d, 1H), 7.53 (dd, 1H), 7.70 (ddd, 1H), 8.65 (d, 1H), 8.77 (dd, 1H); HPLC-MS : mlz = 431.2 (M+1); Rt = 2.79 min.
Example 600 (General procedure 26)
Methyl-phenyl-carbamic acid 4-[2-(1f3-dioxo-1l3-dihydro-isoindol-2-yI)-ethyl]-phenyl ester
The title compound was prepared in 39% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)~phenyl ester and isoindole-1,3-dione. NMR (400MHz; CDCI3): 8 2.98 (t, 2H), 3.41 (br sf 2H), 3.89 (t, 3H), 7.04 (br d, 2H), 7.20-7.40 (m, 7H), 7.68-7.71 (m, 2H), 7.80-7.83 (m, 2H); HPLC-MS : mlz = 401.1 (M+1); Rt = 4.41 min.
Example 601
4-Phenyl-piperidine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyI)-phenyl ester
To a solution of 4-(5-methyl-pyridin-2-ylmethyl)phenol (0.8 mmol) prepared as described above and ethyldiisopropylamine (1.5 mmol) in CH2CI2 (5. mL) at -30 °C was added trichloro-methyl chloroformiate (1.0 mmol). The solution was stirred at -30 °C for 10 min and at reflux

temperature, for 2 h. The solution was evaporated to dryness and redissolved in CH2CI2 (5 mL) and cooled to 0. °C before addition of 4-phenyIpiperidine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated, to give the crude product which was purified
by FC (Quad flash 40 CH2CI2:Et20:Heptane:Et3N 1:1:2:0.25 ->1:1:1:0.25) to give the title
compound in 28% yield as an oil.
1H NMR (400MHz; CDCI3): £1.70-1.80 (mf 2H), 1.91 (br d, 2H), 2.29 (s, 3H), 2.72 (tt, 1H)f
2.94 (br t, 1H), 3.08 (br.t, 1H), 4.10 (s, 2H), 4.42 (br s, 1H), 7.00 (d, 1H), 7.06 (d, 2H), 7.21-7.26 (m, 5H), 7.32 (d, 2H), 7.38 (dd, 1H), 8.37 (d, 1H); HPLC-MS :.m/z= 387.2 (M+1); Rt =
2.95 min.
Example 602
4-(4-Methoxy-phenyl)-3l6-dihydro-2H-pyridine-1-carboxyIicacid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
To a solution of 4-(5-methyl-pyridin-2-ylmethyl)phenol (0.8 mmol) prepared as described above and ethyldiisopropylarnine (1.5 mmol) in CH2CI2 (5 mL) at -30 °C was added trichloro-methyl chloroformiate (1.0 mmol). The solution was stirred at -30 °C for 10 min and at reflux temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2Cl2 (5 mL) and cooled to 0 °C before addition of 4-(4-methoxyphenyI)-1l2,3,6-tetrahydro-pyridine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by FC (Quad flash 40 CH2Cl2:Et20:Heptane:Et3N 1:1:2:0.25 ->1-.1:1:0.25) to give the title compound in 10% yield as colorless crystals. 1H NMR (400MHz; CDCI3): £2.30 (s, 3H), 2.60 (br s, 2H), 3.75-3.88 (m, 5H), 4.12 (s. 2H), 4.20 (br s, 1H), 4.30 (br s, 1H), 5.98 (br s, 1H), 6.88 (d, 2H), 7.00 (d, 1H), 7.07 (d, 2H), 7.24 (d, 2H), 7.34 (d, 2H), 7.39 (dd, 1H), 8.38 (d, 1H); HPLC-MS : mlz= 415.3. (M+1); Rt = 2.95 min.

PHARMACOLOGICAL METHODS
Compounds of formula I may be evaluated in vitro for their efficacy and potency to inhibit HSL, and such evaluation may be performed as described below.
ASSAYS
Hormone-sensitive lipase (HSL)
Materials. The Hormone-sensitive lipase was provided by Dr. Cecilia Holm, from Lund University Sweden or produced and purified by Novo Nordisk (NN) using the reagents and protocols used by Dr. Holm. The substrates used are: 3H-Iabeled triolein (TO) from Amersharn, Buckinghamshire, U.K. cat No. TRA191; 5-20 Ci/mmol dissolved in toluene, triolein (Sigma, Cat. No. T-1740), fluorochrome-Iabeled triacyiglyceride (c/s-octadec-9-enoic acid 2-[12-(7-nitroben2o[1,2)5]oxadiazoI-4"yiamino)dodecanoyIoxy]-1-c/s-octadec-9-enoyloxymethyl-ethyl ester) prepared by Novo Nordisk (NN) by conventional methods, and 1,3-(di[3H]-stearin), 2-(PEG-Biotin)glyceroI prepared in collaboration with Amersharn Pharmacia Biotech, UK and described in WO 01/073442. Phosphatidyl choline (PC) and phosphatidyl inositol (Pi) are from Sigma (St Luis MO cat. Nos. P-3556 and P-5954 respectively). All other reagents are of commercial grade and obtained from various commercial sources.
Methods.
3180.1: Assay for determination of inhibitor IC50 values.
A lipid emulsion with 3H-TrioIein and phospholipid is used as substrate with a standard cencentration of highly purified HSL. BSA is added as product receptor. The substrate is. prepared as follows:
30 pi PC:PI (20 mg/ml solution of PC:PI 3:1 prepared in chloroform) + 128 pi cold TO + 15 pi 3H-TO are mixed and then evaporated under a gentle stream of N2 followed by 20-30 minutes in a Speedvac to ensure the absence of residual solvent.
Compound and HSL are incubated for 30 min at 25 °C before addition of substrate. Reaction is stopped after 30 min at 25 °C by adding a mixture of methanol, chloroform and heptane at high pH. Formed product is separated from substrate by phase separation. Standard concentrations of compound are 100//M, 20//M, 4//M, 0.8//M, 0.16//M and 0.03^/M (sample concentrations). Results are given as IC50 values after 4PL fit of obtained activity data.

3180.2: Assay for determination of percent inhibition by compound at 10//M concentration. A lipid emulsion with 3H-Triolein and phospholipid is used as substrate with a standard cencentration of highly purified HSL. BSA is added as product receptor. The substrate is prepared as follows:.
30 pi PC:PI (20 mg/ml solution of PC:PI 3:1 prepared in chloroform) + 128 pi cold TO + 15 pi 3H-TO are mixed and then evaporated under a gentle stream of N2 followed by 20-30 minutes in a Speedvac to ensure the absence of residual solvent.
Compound and HSL are incubated for 30 min at 25 °C before addition of substrate. Reaction is stopped after 30 min at 25 °C by adding a mixture of methanol, chloroform and heptane at high pH. Formed product is separated from substrate by phase separation. Results are given as percent activity relative to an un-inhibited sample (no compound).
3190.1: Assay for determination of percent inhibition of hormone sensitive lipase by compound at 10pM sample concentration.
A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as substrate with a standard concentration of highly purified HSL (12pg/mL initial concentration cor-. responding to 600ng/mL final concentration), BSA is added as product receptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluorescent properties of the fluorochrome. The changes can be monitored on a fluorimeter with an excitation wavelength of 450nm and an emission wavelength of 545nm. Compound and HSL (20pL compound, 10pL enzyme and 70pL PED-BSA buffer) is pre-incubated for 30min at 25°C before addition of substrate (100yL). Amount of formed product is measured after 120min incubation at 37°C. Results are given as percent activity, relative to a non-inhibited sample (no compound).
3190.2: Assay for determination of IC5o value for the inhibition of hormone sensitive lipase by compound. Standard concentrations of compound are 100//M and 5-fold dilutions (initial concentration corresponding to 10//M final concentration and 5-fold).
A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as substrate with a standard concentration of highly purified HSL (12pg/mL initial concentration corresponding to 600ng/mL final concentration). BSA is added as product receptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluorescent

properties of the fluorochrome. The changes can be monitored on a fluorimeter with an excitation wavelength of 450nm and an emission wavelength of 545nm. Compound and HSL (20JJL compound, 10pL enzyme and 70pL PED-BSA buffer) is pre-incubated for 30min at 25°C before addition of substrate (100pL). Amount of formed product is measured after 120min Incubation at 37°C. Results are given as IC50 values after 4PL fit of obtained activity data.
2848,2: This high-volume screening assay uses para-nitrophenyl butyrate (p-NPB) as substrate for HSL.HSL cleaves p-NPB and the reaction is monitored as an increase in the concentration of para-nitropheno! (p-NP). p-NP can be monitored as an increase in UV-absorbance at 405 nm. The reaction is carried out at room-temp, for 20 min. The action is not stopped, but instead UV-abs is measured at a fixed time (20 min.) Due to autohydrolysis of the substrate the reaction is read at t = 0 min. too and t = 20 min. and the increase in Abs is calculated as the difference between the. two readings. When a compound that inhibits HSL is present, it results in a relative decrease in UV-absorbance.
%Eff (%lnhibition) = (S-SOEff)/(SmaxEff-S0Eff) x 100
Where S = signal in UV-abs., SOEff = assaybuffer alone, SmaxEff = Assaybuffer with the lipase inhibitor.
2898.2: This method is an enzyme assay based upon SPA (scintillation proximity assay) particles. The substrate, 1,3-(di-[3H]-stearin), 2-(PEG-Biotin)-gIyceroI, is marked with 3H in both fatty acid moieties in the tri-glyceride. The third moiety of the tri-glyceride is a PEG linked Biotin. The substrate binds through Biotin to streptavidin in the SPA particles and the proximity between the radioactive tritium in the stearic acid moiety and the SPA particle results in emission of light from the SPA particles. The assay is an on-bead assay where HSL degrades the substrate, where after 3H-stearin acid is released from the bead. The amount of light emitted is proportional to the amount of substrate bound to the receptor. When a compound that inhibits the activity of HSL is present it results in a decrease in degradation of the substrate and thus an increase in the amount of light emitted and a concomitant increase in %Eff.

%Eff (%lnhibitlon) = (S-SOEfQ/(SmaxEff~SOEfF) x 100
Where S = signal in dpm., SOEff = no inhibitor added, SmaxEff» with maximum concentration of inhibitor.






CLAIMS
1. A compound of the general formula II

wherein R1 is selected from Chalky!, C^-alkenyl and C^io-cycioalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sul-fanyl, oxo, halogen, amino, cyano and nitro; and
R2 is selected from C1-6alky!, C2-6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3.10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-8-alkyl, c2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-8-alkyl, C2-8alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl. heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-4-alkyl, C2-6-alkenyl, aryl, heteroaryl, C38-heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C^-alkyl, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci^-alkyl, C2.6-alkenyl, aryl, heteroaryl,. C3-8heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C-alkyl, C2-alkenyl, aryl, heteroaryl, (Wheterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C^-alkyl, C2^-alkenyl, aryl, heteroaryl, C«-heterocyclyl and C3-10-cycloalkyl. is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, CWalkenyl, perhalomethyl and perhalomethoxy, and
wherein R2 is optionally covalently bound to R1 by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1 and R2 are bound; and

R3 is selected from hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6alkenyl, aryl, heteroaryl, C3. e-heterocydyl and c3-c10cycloalkyi, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalky!, (^-alkenyl, aryl, heteroaryl, c1-c6B-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2.6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-io-cycloalkyi is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci-e-alkyi, Qwralkenyl, aryl, heteroaryl, CWheterocyclyl and C3.10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3_1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci-e-alkyi, C2.6-alkenyl, aryl, heteroaryl, C3-s-heterocycIyl and c1-c6crcycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-e-alkenyl, perhalomethyl and perhalomethoxy; and
X is O or S; or
a pharmaceutical^ acceptable salt thereof, or a pharmaceutical^ acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs.
2. A compound of the general formula III


wherein R1a and R23 are independently selected from c1-c6-alkyl, C2.6-alkenyi, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl, each of which is optionally substituted with one or .-more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-silkyt. C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and c1-c6^-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-6-alkyl, C2_8-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano and nitro, Ci-e-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-8alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-10-cycioalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perha-lomethoxy; and
wherein R1a is optionally covalently bound to R2a by an ether, thioether, C-C or C-N bond; to form a ring system with the N-atom to which R1a and R23 are bound; and
R48, R53, R6a and R7a are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3. 10-cycloalkyl, each of which is optionally substituted by one or more substituents selected from hydroxy, sulfanyl, sulfo, oxo, amino, cyano, nitro, c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c1-c6^-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-e-aIkenyl, aryl, heteroaryl, C3_8-heterocyclyl and c1-c6io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perhalomethoxy; and
A1" is N or OR8a; A2* is N or C-R9a; A3a is N or C-R10a; A4a is N or C-R11a; and A5a is N or C-R12a; and
wherein R8a, R93, R10a, R11a and R12a are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, C«-heterocyclyl and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-8-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl and C3.

10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, (^-alkeny!, aryl, heteroaryl, c1-c6-heterocyclyl and C3-1o-cycloaIkyI is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3-e-heterocyclyl and Qj-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-e-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perha-lomethyl and perhalomethoxy.
3. The compound according to claim 2, wherein R23 is phenyl, optionally substituted by halo
gen or methyl.
4. The compound according to any one of claims 2-3, wherein R1a is selected from methyl
and ethyl, optionally substituted by one or more halogen.
5. The compound according to claim 2, wherein R1a and R23 are covalently bound so as. to
form a ring system with the N-atom to which they are bound, wherein said ring system is a
piperidine, piperazine, morpholine, or thiomorpholine.
6. The compound according to any one of claims 2-5, wherein R48, R5a, R6a and R7a are inde
pendently selected from hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -
S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
7. The compound according to any one of claims 2-6, wherein A1a, A23, A38, A43 and A5a are
independently selected from N, CH, CF, C-CI and C-CF3.
8. A compound of the general formula IV


wherein R1b and R2* are independently selected from c1-c6-alkyl, c1-c6alkoxy, c1-c6-aikenyl, aryl, heteroaryl, c1-c6-heterocyc)yl and C3-1o-cycloalkyl, each of which may optionally be substituted with one or more substituents selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-6alkyl, C1-6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d^-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-8-alkyl, C2-8alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6^-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6e-alkyl, C-^-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3.io-cycioalkyl, perhalomethy! and perhalomethoxy;
wherein R1b is optionally covalently bound to R2b by an ether, thioether, C-C or ON bond, to form a ring system with the N-atom to which R1b and R25 are bound;
R56 and R6b are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2.e-alkenyl, aryl, heteroaryl, C3*-heterocyclyI and c3-c10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ct-6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyi, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cydoalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6e-alkyl, perhalomethyl and perhalomethoxy;
R4* and R7* are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, aryl, heteroaryl, c1-c6-heterocycIyl and C3.10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, c1-c6-alkyl, C2-s-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl is optionally substi-

tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, d-e-alkyl, perhalomethyl and perhalomethoxy; and
A1b is N or C-R8b; A2* is N or. C-R9b; A3b is N or OR10b; A4b is N or C-R11b; and A5b is N or C-R12b; and
wherein R8b, R*, R10b, R11b and R12b are selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, Chalky!, C2-6-alkenyl, aryl, heteroaryl, CWheterocyclyl and c3-c10 cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, C2-6-alkenyl, aryl, heteroaryl, C«-heterocyclyl and c3-c10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci-e-alkyi, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3.io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, Ci.6-alkyl, perhalomethyl and perhalomethoxy;
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4b, R5b, RBb, R7b, R8b, R9b, R10b, R11b and R12b.
9. The compound according to claim 8, wherein R2b is phenyl, optionally substituted by halo
gen.
10. The compound according to any one of claims 8-9, wherein R1b is selected from methyl and ethyl, optionally substituted by one or more halogen.
11. The compound according to claim 8, wherein R1b and R2b are covalently bound so as to form a ring system with the N-atom to which they, are bound, wherein the ring system is a piperidine, piperazine, morpholine, or thiomorpholine.
12. The compound according any one of claims 8-11, wherein R4b, R51*, R6b and R7b are independently selected from hydrogen, F, CI, Ci_6-alkyl, c1-c6-alkoxy, -C(0)NH2, -NHC(=0)-OH, -S^O^NH* -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.

13. The. compound according to any one of claims 8-12, wherein A1b, A2b, A3b, A4b and A5b are independently selected from N, CH and CF.
14. A compound of the general formula V

wherein R4c, R5c, R6c, R7c and R8c are independently selected from hydrogen, hydroxy, sul-fanyl, amino, halogen, cyano, suifo, c1-c6-alkyl, Ci-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, c1-c6-alkyl, d^-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-io-cycloalky! may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-i0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6^-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perha-lomethoxy, and
R90, R10G, R11C, R12C and R13c are independently selected from hydrogen, sulfanyl, amino, halogen, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl, wherein each of sulfanyl, amino, sulfo, C1_6-alkyl, c1-c6e-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c3-c10cycloalkyl may optionally be

substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sutfo, c1-c6-alkyl, d-e-alkoxy, C2.e-alkenyl, aryl, heteroaryl, C«-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2-e-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, Cs-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, C3-s-heterocyclyI and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci_e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and pertia-lomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R40, R5°, R60, R7c and R8c; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9c, R10c, R11c, R12c and R13c; and.
at least one of R40, R50, R6c, R7c, R8c, R9c, R10c, R11c, R12c and R13c are different from hydrogen.
15. The compound according to daim 14, wherein R9c, R10G, R11c, R12c and R13c are selected from H and F.
16. The compound according to any one of claims 14-15, wherein R4c, R50, R6c, R7c and R80 are independently selected from hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
17. The compound according to claim 14, where there are no covalent bonds between any of the substituents R9c, R10c, R11c, R12c and R13c.
18. The compound according to any one of claims 14-16, where there are no covalent bonds between any of the substituents R40, R5c, R6c, R7c and R8c.
19. The compound of the general formula


wherein R46 and R5d are independently selected from hydrogen, hydroxy, sulfanyl, amino, C2. e-alkyl, c1-c6-alkoxy, C2-e-alkenyI, aryl, heteroaryl, C3^-heterocyclyl and Ca-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, c1-c6-alkyl, Ci-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, CM-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more sub-stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^-aIkenyl, aryl, heteroaryl, Cs-a-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2^-aIkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, Cs^-heterocydyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R6d, R7df R**, R", R10d, R11d, R12d, R13d and R14d are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, Q^e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-e-aIkenyl, aryl, heteroaryl, C3^-heterocyclyl, and C3_10-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-

alkyl, d-e-alkoxy, C2.e-alkeny!, aryl, heteroaryl, c1-c6-e-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d^-alkyl, d-e-alkoxy, C2-6-alkenyl1 aryl, heteroaryl, c1-c6-heterocyclyl and d-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitre, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, dm-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy:
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R*. R5d, R6d, R7d, R*1 and RM; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10d, R11d, R12d, R13d and R14d.
20. The compound according to claim 19, wherein R4d and R5d are H.
21. The compound according to any one of claims 19-20, wherein R6d, R7d, RBd and RM are selected from the group consisting of hydrogen, F, CI, d-ralkyl, d-e-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
22. The compound according to any one of claims 19-21, wherein R10d, R11d, R12d, R13d and R14d are selected from the group consisting of hydrogen, F, CI, d-e-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
23. The. compound according to any one of claims 19-22, wherein there are no covalent bonds between any of the substituents R4*, R5d, R6d, R7d, RBd and R9d.

24. The compound according to any one of claims 19-23, wherein there are no covalent bonds between any of the substituents R10d, R11d, R12d, R13d and R14d.
25. A compound of the general formula


wherein R4& is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C2-e-alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c68-heterocyciyl and c1-c6io-cycloalkyl, wherein each of c1-c6r-alky!, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the. hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perha-lomethyl and perhalomethoxy; and
R56 is selected from hydrogen, F, cyano, c1-c6-alkyl, d-e-alkoxy, C2^-alkenyt, aryl, heteroaryl, C3-e-heterocyclyl and C3-10-cycloalkyl, wherein each of c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and CiMo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, c1-c6alkoxy, C2_6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1^-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy,

sulfanyi, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, C3-icrcycloalkyl, perhalomethyl and perhalomethoxy;
wherein R40 and R56 may be covalentiy bound to each other by a C-0 bond.
26. The compound according to claim 25, wherein R4e or R5e is selected from the group con
sisting of

wherein R6e, R7\ R8e, R9e and R10e are independently selected from hydrogen, hydroxy, sulfanyi, sulfo, halogen, amino, cyano, nitro, Chalky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyi, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-a-heterocyclyI and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyi, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyi, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6alkenyl.
27. The compound according to claim 25, wherein R4* or R56 is selected from the group con
sisting of.


wherein R6e, R7e, R8e, R9* and R10e are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-io-cycloalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, CWalkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalky!, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Cn-alkoxy and C2^-alkenyl.
28. The compound according to any one of claims 26-27, wherein at least one of the substituents R6e, R7e, R86, R9e and R10e are selected from the group consisting of F and perha-lomethyl.
29. The compound according to claim 25, wherein R4e and R56 are connected by a C-0 bond to form the compound

wherein R11e is selected from hydrogen, hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C1-C6B-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ct-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, ^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10

cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy, and
R12e is selected from hydrogen, F, CI, c1-c6-alkyl, d^-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
30. A compound of the general formula

wherein R4f, R5f, R6f, R7f, R9* and R10f are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, Cswrheterocyclyl and C3-io-cyc!oalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Q^o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2.6-alkenyi, aryl, heteroaryl, c1-c6s-heterocyclyl and C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-e-alkyI, c1-c6-alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, C3-B-heterocyclyi, and Qj-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl, C3-10-cydoaikyl, perhalomethyl and perhalomethoxy: with the proviso that R* and R5f are not both methoxy; and

R8f is selected from hydrogen, sulfo, d-e-alkyl, c1-c6alkoxy, C2.e-alkenyl( aryl, heteroaryl, CW heterocyclyt and c3-c10cycloalkyl, wherein each of sulfo, Chalky!, CWalkoxy, C2-6-alkenyl, aryl, heteroaryl, C«-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, (^-alkeny!, aryl, heteroaryl, C3-8-heterocyclyI, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, perhalomethyl and perhalomethoxy,
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4f, R5f, RBf, Rn and R*; and
wherein there may optionally be a covalent bond between R9f and R10f.
31. The compound according to claim 30, wherein R9f and R10f are covalently bound so as to form a ring system with the C-atom to which they are bound.
32. The compound according to claim 31, wherein said ring system is a cycloalkyl, phenyl, heteroaryl, piperidine, piperazine, morpholine, orthiomorpholine.
33. The compound according to claim 30, wherein R4f and R8f are connected by a C-0 bond to form the compound

wherein R11f is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-10-heterocyclyl and C3-io-cycIoalkyl,

wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6alkenyl, aryl, het-eroaryl, c1-c6-heterocyclyl and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (^.eralkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
R17f is selected from hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2J -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl; and
wherein there may optionally be a covalent bond between R9* and R10f.
34. The compound according to claim 30, wherein R8f is selected from the group consisting
of

wherein R12f, R13f, R14f, R15f and R16f are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6 alkyl, c1-c6-alkoxy, CM-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, CWalkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Q^rheterocyclyl and CS-K,-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI, perhalomethyl and perhalomethoxy.
35. The compound according to claim 30, wherein only R9f and R10f are covalently bound.
36. A compound of the general formula IX


wherein R49, R59, R69, R7g, R*9, R", R100 and R119 are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, c1-c6-alky!, c1-c6-alkoxy, (^B-alkenyl, aryl, het-eroaryl, CM-heterocyclyl and c1-c6io-cycloalkyl, wherein each of c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C-^-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl, and Cs-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6aHcyl. Ci_6-alkoxy, C2-e-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy: and
R129 is selected from the group consisting of -C(=0)-, -C(=0)NH-, -CH2-, -CH2CH2-, -: CHR159-, -CH2CHR15g-, -CHR159-CH2-, -NH-, -NR15g~, -NHC(=0)-, -NR15g-C(=0)-, -O-, -S-, -
S(=OK -s(=o)r;
wherein R15g is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, d-e-alkoxy,. C2^-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-io-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci-e-alkyI, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2^-alkenyl, perhalomethyl and perhalomethoxy; and

wherein there may optionally be one or. more covalent bonds between any of the substituents selected from the group consisting of R49, R5g, R6g, R7fl and R159; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R89, R", R10sf R11fl. and R159; and
R13g is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, c1-c6alkyl, d. e-alkoxy, C2-e-aIkenyl, aryl, heteroaryl, Cw-heterocydyl and C3-io-cycloalkyl, wherein each of C1-6-aIkyl( c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, Cs-e-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, G|_ e-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycIoaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6ralkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, Ca^-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perha-lomethoxy: and
R14g is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C2_6-alkyI, d. 6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of C2_e-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, d-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, d-s-heterocyclyl, and d-10-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, C1r6-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cve-alkyl, C-i-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d-e-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, dwrheterocyclyl and d-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-eralkyl, c1-c6-alkoxy,

C2-6-alkenyl, aryl, heteroaryl, Csj-s-heterocyclyl, C wherein R13fl and R149 may optionally be covalently bound to each other.
37. The compound according to claim 36, wherein R13g and R149 are covalently bound so as to form a ring system with the N-atom to which they are bound.
38. The compound according to claim 37, wherein said ring system is a piperidine, piperazine, morpholine, or thiomorphoiine.
39. The compound according to any one of claims 36-38, wherein there are no covalent bonds between any of the substituents R49, R5s, R69, R79 and R15g.
40. The compound according to any one of claims 36-39, wherein there are no covalent bonds between any of the substituents R* R9g, R109, R11g and R15g.
41. The compound according to any one of claims 36-40, wherein R49, R5g, R69, R7g, Rag, R9g, R109, R119 are selected from the group, consisting of hydrogen, F, CI, d-e-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)z-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
42. A compound of the general formula X

wherein R4h and R5h are independently selected from cyano, c1-c6-alkyl, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or

more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl, and Cs-io-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl, and c3-c10cycloalkyl may optionally be substituted with one or more, substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-nrcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and C3-io-cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, Cs-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R6h, R7h, R8h, R9h, R10h, R12\ R14h and R15h are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, c1-c6-alky!, c1-c6-alkoxy, C2.6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, d-e-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, CWalkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R11h and R13h are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, perhalomethyl, perhalomethoxy, C2_6-alkyl, methoxy, Q^ralkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, wherein each of sulfanyl, amino, C2^-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, C3-s-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocycIyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Cn.6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, d-e-alkoxy,

c1-c6-alkenyl, aryl, heteroaryl, C wherein there may optionally be one or more covaient bonds between any of the substituents selected from the group consisting of R4h, R* R6h, R7\ R8h, R9h; and
wherein there may optionally be one or more covaient bonds between any of the substituents selected from the group consisting of R10h( Rl1h, R12h, R13h, R14h and R15h.
43. The compound according to claim 42, wherein R6h, R™, R8*1, R9h, R10h, R12h and R14h are selected from the group consisting of hydrogen, F, CI, Ci-ralkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0>2-NH2l -NH-S(=OVOH, hydroxy, amino and perhalornethyl.
44. The compound according to. any one of claims 42-43, wherein there are no covaient bonds between R4h, R5h, R6\ R7h, R8h and R9h.
45. The compound according to any one of claim 42-44, wherein there are no covaient bonds between R10h, R11h, R12h, R13\ R14h and R15h.
46. The compound according to any one of claims 42-45, wherein R15h is hydrogen.
47. The compound according to any one of claims 42-46, wherein R11h and R13h are selected from the group consisting of hydrogen, F, CI, C2-6-alkyl, methoxy, c1-c6-alkoxy, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalornethyl.
48. A compound of the general formula


Rs is selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, CWalkyl, c1-c6 alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, wherein each of Ci-e-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.io-cycloalkyl may. optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6B-alkyl, d-e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2_6-alkenyl, aryl, heteroaryl, Qj-s-heterocyclyl, and Cs.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C-^-alkyl, c1-c6alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, c1-c6-alkoxy, C2^-alkenyI, aryl, heteroaryl, (W heterocyclyl, and c1-c6^-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6 alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl, c3-c10cycloalkyl, perha-lomethyl and perhalomethoxy: and
R6i, R71, R*, R9i, R101, R1* and R15i are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Ca-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6e-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, Qj-s-heterocyclyU and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6ralkyl, Ci_6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3.8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci_e-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R11i and R13i are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6alkyl, methoxy, C3-6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of sulfanyl, sulfo, c1-c6-alkyl, CsMi-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,

amino, cyano, nitro, sulfo, Cj-e-alkyl, d-ralkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C*.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d-e-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and d-io-cycloalkyl may optionally be substituted with one. or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2^»alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ga-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R12 is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, d^-alkoxy, C2-e-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-6-alkyl, d-ralkoxy, c1-c6-alkenyl, aryl, heteroaryl, d-s-heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d^alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C&.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyi, d-ralkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Ci-e-alkyI, d-e-alkoxy, d-e-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and c1-c6Krcycloalkyl, perhalomethyl and perhalomethoxy.
49. The compound according to claim 48, wherein R6i, R71, R8' and R91 are selected from the group consisting of hydrogen, F, CI, d^-alkyl, d-ralkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)z-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
50. The compound according to any one of claims 48-49, wherein R101, R11i, R12i, R131 and R14i are selected from the group consisting of hydrogen, F, CI, Chalky!, d-ralkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
51. The compound according to any one of claims 48-50, wherein R1S is hydrogen.
52. The compound according to any. one of claims 48-50, wherein R10i, R11i, R12, R13i, R14i and R15i are selected from the group consisting of H, F and methyl.
53. A compound of the general formula


wherein R4', R^', R6j, R71, R8j, R9j and R10j are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyi, c1-c6-alkoxy, C2_6-alkenyl, aryl, het-eroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6 alkyl, c1-c6alkoxy, C2-6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, Qj-s-heterocyclyl, C3.10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be a covalent bond between the. substituents RBi and R73; and
wherein there may optionally be a covalent bond between Rg and R8]; and
R11Jand R1^ are independently selected from cyano, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6e-heterocyclyl and C3-io-cycloalkyl, wherein each of c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, CM-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted

with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyl, c1-c6-alkoxy, C2_6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and Gs-io-cycloalkyl, perhalomethyl and perhalomethoxy; and
with the proviso that R9j and R10j are both hydrogen, there may optionally be a covaient bond connecting R11iand R1^.
54. The compound according to claim 53, wherein R*j, Rs, R6j and R7* are selected from the group consisting of hydrogen, F, CI, d^-alkyl, C-^-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OHf hydroxy, amino and perhalomethyl.
55. The compound according to any one of claims 53-54, wherein at least one of the substituents R4*, R**, R6J and R73 are different from hydrogen.
56. The compound according to claim 53, wherein R8i is covalently bound to R^.
57. A compound of the general formula

wherein R4* is selected from hydrogen, hydroxy, sulfanyl, sulfo; halogen, amino, cyano, nitro, c1-c6e-alkyl, Ci.6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci_6-alkyl, c1-c6-alkoxy, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, C-^-alkoxy, C2^-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,

amino, cyano, nitro, sulfo, d-e-alkyl, d-e-alkoxy, C2.6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and dt-10-cycloalkyl, perhalomethyl and perhalomethoxy: and
Ra is selected from hydroxy, suffanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkoxy, C2^-alkenyI, aryl, heteroaryl, d-e-heterocyclyl and Cs-io-cydoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, d-e-alkoxy, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-6-alkyl, d-e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Gs^o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, d-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, d-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, dwrheterocyclyl and C3-10-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, d-e-alkoxy, C2-6~ alkenyl, aryl, heteroaryl, d-e-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, d-e-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and c3-c10cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that when R4k is hydrogen, then R5* is not C(=0)N(Me)2; and
R6k, R7kf R8k, R9k, R10k, R11k, R13k and R14k are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyI and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, d-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3-e-heterocycIyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, d-e-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and d-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, d-e-alkoxy, d-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, d-e-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
R12k is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, cyano, nitro, d-e-alkyl, d-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, d-e-heterocyclyl and c3-c10cycloalkyl, wherein each of

hydroxy, sulfanyl, sulfo, amino, Ci-e-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C&r heterocyclyl and C3-io-cycloalkyl may optionally be. substituted with one or more substituents independently selected from hydroxy, sulfanyl, halogen, amino, cyano, n'rtro, sulfo, c1-c6alkyl, Ci_6-alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and c1-c6io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C1.6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci_6-alkyl, c1-c6alkoxy, C2-e-alkenylr aryl, heteroaryl, C3-8-heterocydyl and c3-c10cycloalkyl, perhalomethyl and perhalomethoxy. and
wherein there may optionally be a covalent bond between any of the substituents selected from the group consisting of R4k, R5k, R7* and R8k; and
wherein there may optionally be a covalent bond between R5k and any one of the substituents R7* and R8k; and
wherein there may optionally be one or more covalent bonds between R10k, R11k, R12\ R13k and R1458. The compound according to claim 57, wherein the substituents R4k and R5k are connected by a covalent bond.
59. The compound according to any one of claims 57-58, wherein the substituents R5* and R8k are connected by a covalent bond.
60. The compound according to any one of claims 57-59, wherein the substituents R10k and R11k are connected by a covalent bond.
61. The compound according to any one of claims 57-60, wherein the substituents R12k and R13k are connected by a covalent bond.
62. The compound according to any one of claims 57-61, wherein R6k, R7k, R8k and R9k are selected from the group consisting of hydrogen, F, CI, hydroxy, amino, methyl, methoxy, eth-oxy and perhalomethyl.

63.. The compound according to any one of claims 57-59, wherein R10k, R11k, R12\ R13k and R14k are selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, C-^-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH»S(=0)rOH( hydroxy, amino and perhalomethyi.
64. A compound of the general formula

wherein R1 is c1-c6-alkyl, c1-c6-alkenyl or c1-c6io-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and
R2 is c1-c6alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, or C3-io-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6alkyl, c1-c6alkenyl, aryl, heteroaryl, 0*. s-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, amino, c1-c6-aikyl, Q2-6-alkenyl, aryl, heteroaryl,. C3_8-heterocyclyl and C3-io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo,. halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3.8-heterocyclyl and C3-io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, perhalomethyi and perhalomethoxy; with the proviso that when R1 and R2 are identical they are not methyl or benzyl; and
R2 is optionally covalently bound to R1 by an ether, thioether or C-C bond, to form a ring system with the N-atom to which R1 and R2 are bound; and
Ra, R61, R81, R9V R101 and R111 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, Ci_6-alkoxy, C2^alkenyl, aryl, heteroaryl, C3-8-

heterocydyl and C3_10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, (1^.6-aIkoxy, c1-c6eralkenyl, aryl, heteroaryl, c1-c6rheterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2.6-aIkenyl, aryl, heteroaryl, C3-e-heterocyclyl, and C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 e-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C-^-alkoxy, C2^alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CjMo-cycloalkyl, perhalomethyl and perhalomethoxy. and
R41 and R71 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, methoxy, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of sulfanyl, sulfo, amino, c1-c6-alkyl, C3-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3*-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents. selected from the group consisting of R41, Ra, R61, R71, R81, R91, R101 and R111.
65. The compound according to claim 64, wherein R1 and R2 are covalently bound so as to form a ring system with the N-atom to which they are bound.
66. The compound according to claim 65, wherein said ring system is a piperidine, piperazine, morpholine, or thiomorpholine.
67. The compound according to claim 64, wherein there are no covalent bonds between R1 and R2.

68. The compound according to any one of claims 64-67, wherein there are no covalent bonds between Ra and any of the substituents selected from the group consisiting of R91, R101, R11'.
69. The compound according to any one of claims 64-68, wherein there are no covalent bonds between R8! and any of the substituents selected from the group consisting of R4', R51, R61 and R71.
70. The compound according to any one of claims 64-69, wherein there are no covalent bonds between any of the substituents R41, R51, R61, R71, R8!, R91, R10' and R111.
71. The compound according to any one of claims 64-70, wherein R41, Ra, R61 and R71 are selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, Ci-e-alkoxy, -C(=0)NH2( -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
72. A compound of the general formula

wherein R4m is selected from hydrogen, sulfo, c1-c6-alky!, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, wherein each of sulfo, C1^-alkyl, c1-c6-alkenyl, aryl, het-eroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, CWheterocyclyl, and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, c1-c6-alkoxy, c1-c6-

alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2-6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2^alkenyl, aryl, heteroaryl, CWheterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cn^-alkyl, CWalkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy,, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perha-lomethoxy: and
R5m, R6m, R7m, R8m, R9m, R10m, R11m, R12m, R13m, R14m, R15mand R16m are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, Ci_6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1_6-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.nrcycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2^-aIkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl, and C3-io-cycIoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyi, and C3_io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.10-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4m, R5n\ R6m, R7m and R8m; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9m, R10m, R1lm, R12m, R13m, R14m, R15m and R16m.
73. The compound according to claim 72, wherein there are no covalent bonds between any of the substituents selected from the group consisting of R5m, R6m, R7m and RBm.

74. The compound according to any one of claims 72-73, wherein there are no covalent bonds between any of the substituents R9"1, R10m, R11m, R12m and R13m.
75. The compound according to any one of claims 72-73, wherein there are no covalent bonds between any of the substituents R14m, R15m and R16m.
76. The compound according to any one of claims 72-75, wherein R4m is covalently bound to
R6m..
77. The compound according to any one of claims 72-75, wherein R5m, R6m, R7m, R8m, R9m, R10m, R11m, R12m, R13m and R14m are selected from the group consisting of hydrogen, F, CI, Ci-B-alkyl, d-e-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyi.
78. The compound according to any one of claims 72-77, wherein R14m, R15m and R18m are selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyi.
79.. A compound of the general formula

wherein R4" is selected from hydrogen, sulfo, C2_e-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl, wherein each of sulfo, C2_6-alkyI, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and Qj-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyi,

wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, d-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, d-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3. to-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, d-e-alkoxy, C2^-afkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alky^ c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-hetero-cyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, Ci-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyI, perhalomethyl and perhalomethoxy; and
Z is selected from S, S(=0) and S(=0)2; and
R5n, R6n, R7n, R8n, R9n, R10n, R11n, R12n, R13n and R14n are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C-^-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heteroc1-c6clyl and CjMo-cycIoalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-aikoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-^cloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci_e-alkoxy, CWalkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^»alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6 alkyl, c1-c6alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, C3_s-heterocyclyl and c3-c10cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4n, R5", R6n, R7n and R8n,; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10n, R11n, R12n and R14n; and

at least one of the substituents R5n, R6n, R7n, R8n, R9n, R10n, R11n, R12n, R13n and R14n are different from hydrogen.
80. The compound according to claim 79, wherein there are no covalent bonds between any of the substituents R5n, R6n, R7n and R8n.
81. The compound according to any one of daims 79-80, wherein there are no covalent bonds between any of the substituents R10n, R11n, R12n.
82. The compound according to any one of claims 79-81, wherein R14nis not covalently bound to any other substituent selected from the group consisting of R4n, R5n, R6n, R7nf R8nr
plOn D"l1n p!2n
83. The compound according to any one of claims 79-82, wherein R4n is covalently bound to R6n.
84. The compound according to any one of claims 79-82, wherein R5n, R6n, R7n and R8n are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
85. The compound according to any one of claims 79-84, wherein R14n is selected from the group, consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=O)-0H, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
86. A compound of the general formula

wherein R20 is selected from sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycly! and c1-c6no-cycloalkyl, each of which may optionally be substituted with one or more substitu-

ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suffo, CLs-alkyl, c1-c6-alkoxy, C2,6-aIkeny[, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyI> wherein each of the hydroxy, sulfanyl, amino, suffo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-aIkenyII aryl, heteroaryl, C3-6-heterocyclyI, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, C3. 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, c1-c6-alkenyi, aryl, heteroaryl, c1-c6r heterocyclyl, c3-c10cydoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C-i-e-alkoxy, C2„6-alkenyI, aryl, heteroaryl, Q^s-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R20 is not methyl; and
R40, R5°, R60 and R70 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyi, c1-c6ralkoxy, C2^alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, Cve-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, CWheterocycIyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-to-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d. e-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3-B-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
A10 is N or C-R80; A20 is N or OR90; A30 is N or C-R100; A40 is N or C-R110;. and A50 is N or C-
R120; and
wherein R80, R90, R100, R110 and R12° are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Qwo-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl,

C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c1-c6io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d^-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, Cs-a-heterocyciyf and c3-c10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyl, c1-c6alkenyl, aryl, heteroaryl, Q^rheterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, C2„6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cydoalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, per-halomethyl and perhalomethoxy; with the proviso that
when A1°, A20, A30, A40 and A50 are all CH, and R40, R50, R60 and R70 are all hydrogen, then R2° is not phenyl; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R40, R50, R60, R7°, R8°, R9°, R100, R110 and R120
87. The compound according to claim 86, wherein there are no covalent bonds between any of the substituents R40, R50, R60 and R70.
88. The compound according to any one of claims 86-87, wherein there are no covalent bonds between any of the substituents A10, A20, A30, A40 and A50.
89. The compound according to any one of claims 86-88, wherein R^is selected from the group consisting of cycloalkyl, phenyl, piperidine, piperazine, morpholine, thiomorpholine and heteroaryl.
90. The compound according to any one of claims 86-89, wherein R40, R5°, Reo and R70 are independently, selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
91. A compound of the general formula


wherein R4p is selected from hydrogen, sulfo, C2_6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of sulfo, C2.$-aIkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl rnay optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Cn^-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3_s-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and Cs-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C-^-alkoxy, C2^-alkenyI, aryl, heteroaryl, c1-c6s-heterocyclyl, C3-io-cydoalkyl, perhalomethyl and perhalomethoxy: and
R5p, R6p, R7p and R^ are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6^-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, C3^-heterocyclyl, and Cs-to-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C«-

alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloafkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo( halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl,. c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, Cs-to-cycloalkyf, perhalomethyl and perhalomethoxy; and
R9p, R10p, R11p, R12p, R13p, R14p, R15pand R16p are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, c1-c6-alkoxy, c1-c6e-alkeny!, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cydoalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, Ci-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3^-heterocyc!yl and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2-e-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, d-e-alkoxy, C2-e-alkenyl, aryl, heteroaryl, Cw-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5p, R8p and R7p; and
wherein there may optionally be a covalent bond between R4p and R5p so as to form a chromen ring system; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R* R10p, R11p, R12p, R13p, R14p, R15pand R16p; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2-, -NR17p- and -CR17pR18p-; and
wherein R17p and R18p are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and c1-c6crcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, Ct-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl,

oxo, halogen,, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, Cu-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI, and c1-c6trcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d. 6-alkyl, c1-c6-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl, and C3-io-cycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2^-aikenyl, aryl, heteroaryl, C3-s-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d-e-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci_e-alkyl, c1-c6-alkoxy, d-e-alkenyl, aryl, heteroaryl, Q^-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6 alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy.
92. The compound according to claim 91, wherein E is selected from the group consisting of -O- and -CR17pR18p-.
93. The compound according to claim 91, wherein R4p and R5p are connected by a covalent bond so as to. form said chromen ring system.
94. The compound according to claim 93, wherein R4p and R5p are. connected by a covalent bond so as to form the chromen ring system
i

wherein R19p is selected from the group consisting of hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6s-

heterocyclyl and C3-i0-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, Cve-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyI, Ci-e-alkoxy, C2^alkenyl, aryl, heteroaryl, C3-rheterocyclyI, C3-io-cycloalkyI, perhalomethyl and perhalomethpxy.
95. The compound according to any one of claims 91-92, wherein R4p is selected from the
group consisting of

wherein R20*, R21p, R2^, R239 and R24p are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl and c3-c10cydoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyI, aryl, heteroaryl, C3-s-heterocyc!yl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkoxy, C2-6-alkenyl, perhalomethyl and perhalomethoxy.
96. The compound according to any one of claims 91-92, wherein there are no covalent bonds between any of the substituents R4p, R5p, R6pt R7p and R8p.
97. The compound according to any one of claims 91-96, wherein there are no covalent bonds between any of the substituents R9p, R10p, R11p, R12p, R13p, R14p, R15pand R16p.

98. The compound according to any one of claims 91-96, wherein R10p and R11p are connected by a covalent bond.
99. The compound according to claim 91-97, wherein R9p, R10p, R11p, R12p, R13p, R14p, R15pand R16p are independently selected from hydrogen, F, CI, C-i.e-alkyl, d-e-alkoxy, -C(=0)IMH2, -NHC(=0)-OH) -S(=0)2-NH2| -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.

100. The compound according to any one of claims 91, 92,95-99, wherein R5p, R6p, R7p and RBp are independently selected from hydrogen, F, CI, c1-c6-aikyl, c1-c6-alkoxy, -C(=0)NH2, -NHc1-c6OJ-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
101. A compound of the general formula

wherein R4q, R6q, R7q, R9q, R10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q,and R18q are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalky!, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyl may optionally be substituted with one or more sub-st'rtuents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d-e-alkoxy, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, CW-alkenyl, aryl, heteroaryl, C3-B-heterocyclyl, C3.i0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and C3_10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3*-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d^-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, C3^-heterocycIyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C«-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy: and

R5* and R8* are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, Br, amino, cyano, nitro, c1-c6-alkyl, d-e-alkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2_6-alkenylr aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo, c1-c6-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl,'C3_8-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-B-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.e-a!kenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perha-lomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Ft4*, R5q, R6q, R7q and R8* and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9q, R10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q and R18q.
102. The compound according to claim 101, wherein R^ and R6q are connected by a covalent bond.
103. The compound according to claim 101, wherein R^ is selected from the group consisting of substituted heteroaryl and substituted C3-s-heterocyclyl.
104. The compound according to any one. of claims 101 and 103, wherein R4q is selected from the group consisting of


wherein R19q, R20q, R™\ R22* and R23" are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, het-eroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl, G^-alkoxy, c1-c6-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently, selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Cve-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci_6-alkylf c1-c6e-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, CM-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy.
105. The compound according to any one of claims 101 and 103-104, wherein there are no covalent bonds between any of the substituents R4^ R5q, R6q, R7q and RBq.
106. The compound according to any one of claims 101-105, wherein there are no covalent bonds between any of the substituents R9q, R10q, R11q, R12q, R13q, R14q, R15q' R16q, R17q and R18q.
107. The compound according to any one of claims 101-105, wherein R10p and R11p are connected by a covalent bond.
108. The compound according to any one of claims 101-105, wherein R11p and R13p are con
nected by a covalent bond.

109. The compound according to any one of claims 101-106, wherein R9q, R10q, R11q, R12q,
R13qf R14q( R15q, R16q, R17q and R18q are independently selected from hydrogen, F, CI, c1-c6
alkyl. c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=OyOH, hydroxy, amino
and perhalomethyl.
110. The compound according to any one of claims 101-106 and 109, wherein R9q, R10q,
R11q, R12qf R14q, R15q, R16qt R17q and R18q are all hydrogen or F.
111. The compound according to any one of claims 101 and 103-110, wherein R^, R6qf R7q and R8q are independently, selected from hydrogen, F, CI, c1-c6-alkyl, d-e-alkoxy, -C(=0)NH2> -NHC(=0)-OH, «S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
112. A compound of the genera! formula

wherein R^ is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d^-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C-j-6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, sulfo, Ci-e-alkyI, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl, C3-to-cycloalkyl, perhalomethyl and perhalomethoxy: provided that R4ris not methyl or phenyl; and

R* R6r, R7r, R8r, R9r, R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17p and R18r are independently selected from hydrogen, hydroxy, sulfanyl, sulfa, F, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, whereia each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl, d^-alkoxy, c1-c6e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-. alkoxy, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-i0-cycloalkyl, perha-lomethyl and perhalomethoxy: and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5r, R6r, R7r and R8r; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9r, R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17r and R18r.
113. The compound according to claim 112, wherein R* and R5r are connected by a covalent
bond.
114. The compound according to claim 112, wherein R4r is selected from the group consist
ing of substituted heteroaryl and substituted c1-c6s-heterocyclyl.
115. The compound according to any one of claims 112 and 114, wherein R4r is selected
from the group consisting of

wherein R19r, R20r, R21r, R2* and R23' are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, d-e-alkoxy, C2^-alkenyl, aryl, heteroaryl,

d-e-heterocyclyl and c3-c10cycioalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1BC-alkyl, d-e-alkoxy, d-e-a'kenyl, aryl, heteroaryl, c1-c6-heterocydyl and d-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, d-r-alkyl,. d-6-aIkoxy, C2-e-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-s-alkyl, c1-c6-alkoxy, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CMO-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, d-s-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, d-a-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, G^-alkoxy, d^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Qt-6-aIkyl, d-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, d-8-heterocyclyl, c3-c10cycloalkyl, perha-lomethyl and perhalomethoxy.
116. The compound according to any one of claims 112-115, wherein there are no covalent bonds between any of the substituents R5r, R6r, R7r and R8r.
117. The compound according to any one of claims 112-116, wherein there are no covalent bonds between any of the substituents R* R10rf R11r, R12r, R13r, R14r, R15r and R16r.
118. The. compound according to any one of claims 112-116, wherein R10r and R11r are connected by a covalent bond.
119. The compound according to claim 116, wherein R11r and R13r are connected by a covalent bond.
120. The compound according to any one of claims 112-116, wherein R9r, R10r, R1lr, R12r, R13r, R14r, R15r, R16r, R17r and Rn8r are independently selected from hydrogen, F, CI, d-e-alkyl, d-e-alkoxy, -C(=0)NH2l -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=O)r0H, hydroxy, amino and perhalomethyl.
121. The compound according to any one of claims 112-117 and 120, wherein R9r, R10r, R11r, R12r, R14r, R15r, R16r, R17r and R18r are all hydrogen or F.

122. The compound according to any one of claims 112 and 114-121, wherein R5r, RBr, R7r and R8r are independently selected from hydrogen, F, CI, Chalky!, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0);rOH, hydroxy, amino and pertnalomethyl.
123. A compound of the general formula

wherein A1s is N or C-R17s; A25 is N or C-R18s; A3s is N or C-R19s; A4s is N or C-R20s; and A5s is N or C-R21s; and
wherein R17s, R18s, R19s, R20s and R21s are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_s-heterocycIyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyi is. optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6e-alkyl, C2^-alkenyl, aryl, heteroaryl, CWheterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyU aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C-^-alkyl, C2^alkenyl, aryl, heteroaryl, Oj-s-heterocyclyl and c1-c6io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, Cs-io-cycloalkyl, perhalomethyl and perhalomethoxy; and

R5s, R68, R7s and R8s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cw-heterocyclyl and Cs-io-c1-c6cloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.e-alkenyl, aryl, heteroaryl, c1-c6r heterocyclyl, and C3-io-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-e-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl, and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^alkenyl, aryl, heteroaryl, c1-c6e-heterocyclyl, CiMcrcycloalkyl, perhalomethyl and perhalomethoxy: and
R9S, R10s, R11s, R12s, R13s, R14s, R15s and R16s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3_a-heterocyclyl and C3-io-cycIoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2.e-alkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, Ci-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6^-cycloalkyl, perhalomethyl and perhalomethoxy: and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2-, -NR225- and -CR^R235-; and
wherein R225 and R23s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alky!, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, d-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, CWalkoxy, (Walkenyl, aryl, heteroaryl,

c1-c6B-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfany!, amino, sulfo, d. e-alkyl, c1-c6-alkoxy, (W-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycloaIkyl may optionally be substituted with one. or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyl, c1-c6-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl, C3-io-cycIoaIkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R58, R68, R7s and R8s; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9s, R10s, Rl1s, R12s, R13s, R14s, R15s, R16s, R18s. R19s, R208, R21s, R226 and R235.
124. The compound according to claim 123, wherein E is selected from the group consisting of.-O-and-CR^R235-.
125. The compound according to any one of claims 123-124, wherein there are no covalent bonds between any of the substituents R5s, R6s, R7s and RBs.
126. The compound according to any one of claims 123-125, wherein R5s, R6s, R7s and R8s are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, Ci_e-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
127. The compound according to any one of claims 123-126, wherein there is a covalent bond between R10s and R11s.
128. The compound according to any one of claims 123-127, wherein there is a covalent bond between R13s and R228.
129. The compound according to any one of claims 123-126, wherein R9s, R10s, R11s, R128, R13s, R14s, R15s and R16s are all hydrogen or R
130. A compound of. the general formula


wherein E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0>2-, -NR18t- and -CR18tR19t-; and
R41, R5t, Rm, R7t, R*, R91, R10t, R1tt, R12t, R131, R14t, R15t, R16t, R17t, R18t and R19t are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and C3-io-cycIoalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl and C3_i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, d-e-alkyl, c1-c6e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, d-e-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-B-heterocydyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, C-j-e-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, Ci-e-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, C3-8-heterocyc!yl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R4t and R5t are not both methyl; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9t, R10t, R11t, Riat R13t, R14t, R15t, R16t, R17t,R18t and R19t.

131. The compound according to claim 130, wherein E is selected from the group consisting of -0-, -S-, -S(=OH -S(=0)r and -CR18lR19t-.
132. The compound according to any one of claims 130-131, wherein R18t is hydrogen or F.
133. The compound according to any one of claims 130-132, wherein R10t, R12t, R4t and R61 are all hydrogen.
134. The compound according to any one of claims 130-132, wherein R6t, R7t, R8t and R91 are independently selected from the group consisting of hydrogen, F, CI, C-i-e-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
135. The compound according to any one of claims 130-134, wherein there is a covalent bond between R11t and R131.
136. The compound according to any one of claims 130-135, wherein there is a covalent bond between R13t and R19t.
137. The compound according to any. one of claims. 130-134, wherein R10\ R11t, R12t, R13t, R14t, R15t, R16t and R17t are all hydrogen or F.

wherein R4u, R5u, R6U, R7u, R8u, R90, R10u, Rl1u, R12u( R13u, R14u and R15u are independently selected, from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c1-c6crcycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-8-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6Krcydoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (^-alkenyl, aryl, het-eroaryl, C3-8-heterocyclyI, and c1-c6io-c1-c6cloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni-tro, sulfo, d^-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-e~heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C-^-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, c1-c6Krcycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that R4", R5u and R6u are not all hydrogen; and
E is selected from the group consisting of -0-, -S-, -S(=0>, -S(=0)2-, -NR16u- and
_CR16UR17US
wherein R16u and R17u are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6e-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3_i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyI, aryl, heteroaryl, CM-heterocyclyl, and C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d. 6-alkyl, C-i-e-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci.6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4u( R5u and R6u; and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R8u, R9u, R10u and R11u; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R12u, R13u, R14u, R15u, R16u and R17u.
139. The compound according to claim 138, wherein E is selected from the group consisting of -0-, -S-, -S(=Oh -S(=0)2- and -CR16uR17140. The compound according to any one of claims 138-139, wherein R17u is hydrogen or F.
141. The compound according to any one of claims 138-140, wherein there are no covalent bonds between any of the substituents R8U, R90, R10u and R11u.
142. The compound according to any one of claims 138-141, wherein R8u, R9u, R10u and R11u are independently selected from the group consisting of hydrogen, F, CI, d-e-alkyl, Ci-e" alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0}2-NH2, -NH-S(=0)2-OH, hydroxy, amino and per-halomethyl.
143. The compound according to any one of claims 138-142, wherein there is a covalent bond between R12u and R13u.
144. The compound according to claim 138-142, wherein R12u, R13u, R14u and R15u are all selected from the group consisting of hydrogen, F, methyl and c1-c6-alkyl.
145. A compound of the general formula


wherein R4v, R5*, R6v, R7\ R8v, R9*, R10v, R11v, R12v, R13v, R14v, R15v, R16v, R17v and R18v are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C-i-e-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, Ci.B-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-s-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, c1-c6e-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6e-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocydyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyIf aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6e-alkyl, c1-c6-aikoxy, C2^-alkenyl, aryl, heteroaryl, CM-heterocycIyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that none of the substituents R4v, R5v and R6v are benzothiazolyl or benzooxazolyl; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2-, -NR19v- and. -CR^R**-; and
wherein R19v and R20v are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alky!, (Walkenyl, aryl, heteroaryl, CM-heterocyclyl and C3.

io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-alkenyI, aryl, heteroaryl, Cs-s-heterocyclyl, and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-B-heterocycfyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci_6-alkyl, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy, and
wherein there may optionally be a covalent bond between the substituents R7v and R8v or between the substituents R9* and R10v; and
wherein there may optionally be a covalent bond between R6v and a substituent selected from R8v and R9*; and
wherein there may be a covalent bond between any of the substituents selected from the group consisting of R4v, R5v and RSv; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R"v, R12v, R13v, R14v, R15v, R16v, R17v, R18v, R19v and R20v.
146. The compound according to claim 145, wherein E is selected from the group consisting of -0-, -S-, -S(=Oh -S(=0)2- and -CR19vR20v-.
147. The compound according to claim 145, wherein R20v is hydrogen or F.
148. The compound according to any one of claims 145-147, wherein there are no covalent bonds between any of the substituents R4vf R5v and R6*.
149. The compound according to any one of claims 145-148, wherein there are no covalent bonds between any of the substituents R7v, R8v, R9* and R10v.

150. The compound according to any one of claims 145-149, wherein there are no covalent bonds between a substituent selected from the group consisting of R4v, R5v and R6v and a substituent selected from the group consisting of R7v, R8v, R9v and R10v.
151. The compound according to claim 145-150, wherein R7v, R8v, R9v and R10v are independently selected from the group consisting of hydrogen, F, CI, Chalky!, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.

152. The compound according to claim 145-151, wherein there is a covalent bond between R12v and R13v.
153. The compound according to any one of claims 145-151, wherein R11v, R12v, R13v, R14v, R15v, R16v, R17v and R18v are all hydrogen or F.
154. A compound of the general formula

wherein R4w is selected from hydrogen, hydroxy, amino, suifo, c1-c6alkyl, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, amino, sulfo, Chalky!, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and C$.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, (^-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci_e-alkyl, c1-c6alkoxy, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Quo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2^-alkenylf aryl, heteroaryl, C3.B-heterocyclyl and Cs-io-cydoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci. e-alkyl, Ci_6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl, and Cs-io-cycloalkyl may

optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfa, C1-6aikyl, C-^e-aikoxy, C2^-aIkenyi, aryl, heteroaryl, c1-c6-heterocydyl, Cs-io-cycloalkyl, perhalomethyl and perhalomethoxy: with the proviso that R4* is not methyl, morpholine or a 2-chromen derivative; and
Z is selected from S, S(=0) and S(=0)2; and
R*\ R**, R7", R*\ R*", R10w, R11w, R12*, Rn3w, R14w, R15w and R16w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nltro, Ci-r-aJkyl, G>.6-aikoxy, C2-ralkenyl, aryl, heteroaryl, Cs^-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and c3-c10cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and CM0-cycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sutfo, c1-c6-alkyl, C-^-alkoxy, C2^alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and C3-io~cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2.«ralkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CMo-cycloalkyl, perhalomethyl and perhalomethoxy: and
E is selected from the group consisting of -O-, -S-, -S(=0)-, -S(=0)2-, -NR17w- and. -CR17wRl8ws and
wherein R17wand R18w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyi, c1-c6-alkoxy, c1-c6B-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyi, and C3.10-cycloaikyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cv e-alkyl, c1-c6-alkoxy, C2-ralkenyl, aryl, heteroaryl, Cs^-heterocyciyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2-6-alkenyt, aryl, heteroaryl, c1-c6-heterocyciyi, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and

wherein there may optionally be one or more covalent bonds between any. of the substituents selected from the group consisting of R4w, R5", R6w, R7w and R8w; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9w, R10w, R11w, R12w, R13w, R14w, R15w, R16w, R17w and R1Sw.
155. The compound according to claim 154, wherein the only substituents which are cova-lently bound are R4* and R5*.
156. The compound according to any one of claims 154-155, wherein there are no covalent bonds between any of the substituents R* R6w, R7w and R8".
157. The compound according to any one of claims 154-156, wherein there are no covalent bonds between any of the substituents R9w, R10w, R11w, R12w, R13w, R14wt R15w and R16w.
158. The compound according to any one of claims 154-157, wherein E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2- and -CR17wR18w~.
159. The compound according to any one of claims 154-158, wherein R18w is hydrogen or F.
160. The compound according to any one of claims 154 and 156-159, wherein R5*, R6W, R7w and R8* are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy; amino and perhalomethyL
161. The compound according to any one of claims 154,156 and 158-160, wherein there is a covalent bond between R10w and R11w.
162. The compound according to claim 154,156 and 158-161, wherein there is a covalent bond between R13w and R17w.
163. The compound according to any one of claims 154-160, wherein R9*, R10w, R11w, R12w, R13w, R14w, R15w and R16w are all hydrogen or F.

164. A compound of the general formula

wherein R4x is selected from imino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl and C3-io-cycloalkyl, wherein each of imino, c1-c6-alkyl, C2^-aIkenyl, arylf heteroaryl, c1-c6-heterocydyl and C3_io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyII aryl, heteroaryl, Cs_ 8-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^alkenyl, aryl, heteroaryl, Qwrheterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d-e-aikoxy, C2^-alkenyl, aryl, heteroaryl, Ca-s-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, CWalkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6e-heterocyclyl, Qj-io-cycloalkyl, wherein each of the hydroxy, sulfanyl,. amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6alkyl, Ci-e-alkoxy, C2^-alkenyl, pertialomethyl and perhalomethoxy; and
R5x, R6x, R7x, R8x, R9x, R10x, R11x, R12x and R13x are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-aJkyl. c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-i0-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and Cwo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hy-

droxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-aikenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, c1-c6-alkoxy, C2-B-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl, C3.10-cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)r. -NR14x- and -CR15xR16x-;
wherein R14x is selected from hydrogen, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3.to-cycloalkyl, wherein each of sulfo, c1-c6-alky!, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.eralkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and Cs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Cn-e-alkyl, Ci-e-alkoxy, C2_6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, C3-KrcycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, d^-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c610-cycloalkyl, perhalomethyl and perhalomethoxy; and
R15x and R16x are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C-i-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6Krcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, Cs-s-heterocyciyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-i heterocyclyl, and c1-c6io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6

alkyl, C-j-e-alkaxy, c1-c6s-alkenyl, aryl, heteroaryl, C3-s-heterocyclyI, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, d^-alkoxy, C2^-aIkenyl, aryl, heteroaryl, CW-heterocyclyl, C3-10-cycloaIkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4x and R5x; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R6x, R7x, R^ and R9x; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10x, R11x, R12x, R13x, R14x, R15x and R16x.
165.. The compound according to claim 164, wherein R6x, R7x, R8x and R^ are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2»NH2, -NH-S(=0);rOH( hydroxy, amino and perhalomethyl.
166. The compound according to any one of claims 164-165, wherein R10x, R11x, R12x and R13x are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and per-halomethyl.
167. The compound according to any one of claims 164 and 166, wherein there is a covalent bond between the substituents R6x and R7x.
168. The compound according to any one of claims 164-165, wherein there is a covalent bond between the substituents Rnox and Rm.
169. The compound according to any one of claims 164-165 and 167, wherein there is a covalent bond between R10x and a substituent selected from R14x and R15x.
170. A compound of the general formula


wherein R4y and R11y are independently selected from imino, CWalkyl, C2-6-aIkenyl, aryl, heteroaryl, CM-heterocyclyl and c1-c6urcycloalkyl, wherein each of imino, c1-c6-alkyl, C2^-aIkenyIf aryl, heteroaryl, Cs-s-heterocyclyl and dj-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, C2^-alkenylI aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6io-cycloalkyl may optionally, be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, d_e-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3. 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycIoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and QMo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C-^-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, perhalomethyl and perhalomethoxy; and
R5y, R6y, R7y, R8y, R9y and R10y are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C-^-alkoxy, C2-6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-io-cydoalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,'amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-icrcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C,. e-alkyl, c1-c6-alkoxy, c1-c6-s-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyi, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy,

sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkoxy, C2.e-alkenyl, aryl, heteroaryi, CW-heterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-e-alkyI, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryi, c1-c6s-heterocyclyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI1 aryl, heteroaryi, c1-c6-heterocyclyl, C3-i0-cycloalkylf wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyi, aryl, heteroaryi, CWheterocyclyl, and c3-c10cycloalk^ may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryi, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4y and R5y; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R6y R7y, R8y and R9*; and
wherein there may optionally be a covalent bond between the substituents R10y and R11y.
171. The compound according to claim 170, wherein R6y, R7y, R8y and R9* are independently selected from the group consisting of hydrogen, F, CI, C-^-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
172. The compound according to any one of claims 170-171, wherein there are no covalent bonds between any of the substituents R6y, R7y, RBy and R9y.
173. The compound according to any one of claims 170-172, wherein there is a covalent bond between the substituents R4y and R5y.
174. The compound according to any one of claims 170-173, wherein there is a covalent bond between the substituents R10y and R11y
175. A compound of the general formula


'8z
R
wherein R4z, R82, R92, R102, R112, R12z, R132, R142, R152, R162 and R17z are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ct-e-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and C3_io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.i0-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-e-heterocycIyl, and Ca-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and
R52 is a carbon bound substituent selected from c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-io-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and CiMo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, Ci-6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl may optionally

be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cwrheterocyclyl, Cs-no-cycloalkyl, perhalomethyl and perhalomethoxy; and
R62 and R7z are independently selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci-e-alkyl, c1-c6-alkoxy, C2-6-alkeny!, aryl, heteroaryl, c1-c6-heterocycIyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-iQ-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C-^alkoxy, C2.6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloa!kyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 alkyl, c1-c6-alkoxy, C2.e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sutfo, c1-c6-alkyl, c1-c6e-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of -0-, -S-, -S(=0)-, -S(=0)2-, -NR18z- and -CR19^202-;
wherein R1Bz is selected from hydrogen, sulfo, c1-c6-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and Cs-io-cycloalkyl, wherein each of sulfo, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-io-cydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C-^-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycioaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C-wrheterocyclyl, Ca-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, Q^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl may optionally be substituted with one or

more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and
R19z and R2te are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Chalky!, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, C$s-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 alkyl, c1-c6alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6io-cycloalkyi, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4z and R52; and
wherein there may optionally be a covalent bond between any of the substituents R7z, Rte, and R9*; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R10z, Rm, R12z, R13z, R14z, R15z, R16z, R17z, R18z, R19z, and R20*.
176. The compound according to claim 175, wherein there is a covalent bond between the substituents R4z and R5z.
177. The compound according to any one of claims 175-176, wherein R6z, R7z, R8z and R92 are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2f -NHC(=0)-OH, -S(=0)2-NH2| -NH"S(=0)rOH, hydroxy, amino and perhalomethyl.
178. The compound according to any one of claims 175-177, wherein there is a covalent bond between R13z and a substituent selected from R18z and R19z.

179. A compound of the general formula

wherein R433 is selected from hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyi, C2^-alkenyl, aryl, heteroaryl, Qwrheterocyclyl and C3_1crcycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyl» aryl, heteroaryl, C3_8-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycioaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, CsMo-cycloalkyl, wherein each of the. hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, c1-c6-alkoxy, c1-c6alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perha-lomethoxy; and
R5aa, R633, R7aa, R8aa, R933, R10aa, R11aa, R12aa and R13aa are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyciyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyI, aryl, heteroaryl, C-^-heterocyclyl and C3-io-cydoalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C1-6-alkoxy, C2.$-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-io-cycloalkyl, wherein each of the hydroxy, suifanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, ^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.no-cycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6trcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-aIkenyIr aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl* c1-c6-alkoxy, C2-6-aIkenyl, aryl, heteroaryl, C3-e-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R5aa and R6aa or between the substituent R7aa and R8aa; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9aa, R10aa, R11aa and R12aa; and
E is selected from the group consisting of -0-, -S-, -S(=0)- and -S(=0)2-.
180. The compound according to claim 179, wherein there is a covalent bond between the substituents R9aa and R10aa.
181. The compound according to any one of claims 179-180, wherein R5aa, R6aa, R7aa and R8aa are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl, d.e-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)z-OH, hydroxy, amino and perhalomethyl.
182. The compound according to any one of claims 179-181, wherein at least one of the substituents R5aa, R688, R7aa and R8aa are different from hydrogen.
183. A compound of the general formula


wherein R4^ is selected from sulfanyl, sulfo, amino, c1-c6-alkyl, C2-s-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and Gs-io-cycioalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cydoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C1^-aIkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, C3-B-heterocycfyl, C3-«rcydoaIkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C-j-e-alkoxy, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyctyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyi, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; and
E is selected from the group consisting of -NR13ab- and -CR14abR15ab-; and
R5ab, R6ab, R7ab, R8ab, R9ab, R10ab, R11af\ R12ab, R13ab, R14ab and R15ab are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, C«-heterocyclyl and C3-io"Cydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cydoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6a-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2.6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-oycloalkyI, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; and

wherein there may optionally be a covalent bond between the substituents R5ab and R6ab or between the substituent R7aband R8ab; and
wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9ab, R10ab, R11ab, R12ab, R13ab, R14ab and R15ab.
184. The compound according to claim 183, wherein there is a covalent bond between the substituents R9ab and R10ab.
185. The compound according to any one of claims 183-184, wherein there is a covalent bond between R10ab and a substituent selected from R13ab and R14ab.
186. The compound according to any one of claims 183-185, wherein R5ab, R6ab, R7ab and Rteb are independently selected from the group consisting of hydrogen, F, CI, c1-c6»alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=OK>H. -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and per-haiomethyl.
187. The compound according to any one of claims 183-186, wherein at least one of the substituents R5ab, R6ab, R7ab and RBab are different from hydrogen.
188.. The compound according to any one of claims 183-187, wherein at least one of the substituents R^, R10ab, R11ab,.R12ab, R13ab, Ruab and R15ab are different from hydrogen.
189. A compound of the general formula

wherein R4ac is a carbon bound substituent selected from c1-c6-alkyl, c1-c6-alkenyl, arylr het-eroaryl, c1-c6-heterocydyl and Cs-nrcycloalkyl, each of which may optionally be substituted

with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Ca-nrcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ct-e-alkyl, c1-c6-alkoxy, C2„6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, (^-heterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, Cs-s-heterocydyl, and c1-c610-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perha-lomethoxy; and

R5ac, R680, R7ac, R830, R9ac, R10ac and R11ac are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, Ci-e-alkoxy, (Walkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Chalky!, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, C3_g-heterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C1fc6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano,. nitro, sulfo, Ci-e-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that A3ac is not C-C(OH)(CF3)2; and


R12ac and R13ac are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkoxy, C2_6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyi and C3.io-cycloalkyl, wherein each of sulfanyl, sulfo, amino, c1-c6-alkyl, C2-e-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyctyl and C3-i0-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, C-^-alkoxy, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cydoaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one. or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6io-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R4ac and a substituent selected from the group consisting of R5ac and R6aa; with the proviso that A1ac, A230, A3ac, A4ac and A5ac are not ail CH; and
wherein there may optionally be a covalent bond between any of the substituents R6ac, R7ac and R830; and
wherein there may optionally be one or more covalent bonds between any of the substituents in A1ac, A230, A380, A430 and A5ac.
190. The compound according to claim 189, wherein there is a covalent bond between the substituents R430 and R6ac.
191. The compound according to any one of claims 189-190, wherein there is a covalent bond between A3ac and A4ac.
192. The compound according to any one of claims 189-191, wherein there is a covalent bond between A330 and A230.

193. The compound according to any one of claims 189 and 191-192, wherein R530, R6ac, R7ac
and RSac are independently selected from the group consisting of hydrogen, F, CI, c1-c6-alkyl,
c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)rNH2l -NH-S(=0)2-OH, hydroxy, amino and
perhalomethyl.
194. The compound according to any one of claims 189-193, wherein at least one of the sub-
stituents A1aG, A280, A330, A430 and A5ac are different from CH.
195. A compound of the general formula

wherein R43* is selected from hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 alkyl, C-i-e-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ci_6-aIkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, CWalkyl, c1-c6-alkoxy, CWalkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c1-c6io-cycloalkyl, perhalomethyl and perha-lomethoxy; and
R5ad, R5ad, R7ad, R8ad and R9ad are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkoxy, C2^-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl,

c1-c6-alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-1CrcycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-Kj-cycloallcyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cv 6-alkyl, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-icrcycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkylv c1-c6alkoxy, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d.6-alkyl, c1-c6-alkoxy, (Walkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkoxy, C2-6-alkenyl, aryl, heteroaryl* Qj-s-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perha-lomethoxy; and
R10ad are selected from imino, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c1-c6io-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, Ci-e-alkoxy, C2-6«alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-to-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, Ct-e-alkoxy, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, CWalkoxy, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkoxy, C2-6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl, C3-i0-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there'may optionally be a covalent bond between R4** and a substituent selected from R6ad and R7ad; and
wherein there may optionally be a covalent bond between the substituents R9ad and R10ad so as to form a 5-membered ring system.

196. The compound according to claim 195, wherein the substituents R0* and R10ad are co-
valently bound so as to form a 5-membered ring system.
197. The compound according to claim 196, wherein said 5-membered ring system com
prises at least one nitrogen atom in the ring.
198. The compound according to claim 196, wherein said 5-membered ring system contains
5 carbons in the ring.
199. The compound according to any one of claims 195-198, wherein there is a covalent
bond between the substituents R4*1 and R7ad.
200. The compound according to any one of claims 195-198, wherein R5ad, R65"1, R7ad and R8ad are independently selected from the group consisting of hydrogen, F, CI, Ci-6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(-0)-OH, -S(=0)2-NH2l -NH-S(=0)2-OH, hydroxy; amino and per-halomethyl.
201. A compound of the general formula

wherein E is selected from the group consisting of -0-, -S-, -S(=0)-f -S(=0)2-, -NR16ae- and -
CR17aeR1Bae_; and
p4ae p5ae p6ae o7ae pBae p9ae n10ae p11ae p12ae p13ae p14ae p15ae p16ae p1"7ae aprl Rl&as arft
independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci-e-alkyi, c1-c6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently

selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suifo, c1-c6-alkyl, CM-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo, c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6e-heterocycfyl, and Cs-icr cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suifo, c1-c6-alky!, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl, c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suifo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CjMD-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suifo, Ci-e-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, suifo, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between any of the substituents selected from R4ae, R5ae, R6afi and R7ae; with the proviso that when R536 and R636 are covaiently bound they do not form a isoquinolin-3-yl or a substituted isoquinolin-3-yl together with the pyridine which they are both bound to; and
. wherein there may optionally be a covalent bond between any of the substituents selected
from R8a9 P936 p1°a® p11ae p12ae p13ae p14ae n15ae p!6ae p17ae a-j p18ae
202. The compound according to claim 201, wherein there is a covalent bond between R6aB and R7ae.
203. The compound according to claim 201, wherein there is a covalent bond between R5ae and R6ae.
204. The compound according to any one of claims 201-203, wherein at least one of R8ae,
pfl* R10ae( pHa^ R12» R13ae R14ae an(j R15ae js se|ected from F> C|, c1-c6-alkyl, d.6-alkOXy, -
C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
205. A compound of the general formula


wherein R4af, R5*, R6af, R7af( R8af, R9af, R10af, R11af, R12af, R13af, R14af and R15af are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2. e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, CWalkyl, c1-c6-aikenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, Ctj-s-heterocyclyl, CiMo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyi, c1-c6-alkenyl, aryl, heteroaryl, CM-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 alkyl, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocydyl, and C3-io-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, c1-c6io-cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R6af and any of the substituents selected from R5af and R7af; and
wherein there may optionally be a covalent bond between the substituents R9af and R10af; and
R16af is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2.6-alkenyl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or

more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, Ca-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-10-cycioalkyl, wherein each of the hydroxy, sulfanyl*. amino, sulfo, c1-c6-alkyl, C2^»alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, QMo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl9 C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl, and c3-c10cycloalkyl may optionally be substituted with one. or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3_10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, Cae-alkenyl, aryl, heteroaryl, (W heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cn-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and per-halomethoxy; with the proviso that R16af is not methyl; and
wherein there may optionally be a covalent bond between the substituents R12af and R16af.
206. The compound according to claim 205, wherein there is a covalent bond between the substituents R" and R6af.
207. The compound according to any one of claims 205-206, wherein there is a covalent bond between the substituents R9af and R10af.
208. The compound according to any one of claims 205-207, wherein at least one of R8af, R9af, R10af, Rl1af, R12af, R13af, R14af and R15af is selected from F, CI, c1-c6alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2l -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
209. A compound of the general formula


wherein E is selected from the. group consisting of -0-, -S-, -S(=0)-, -S(=0)z- and -
CR16agR17ag-; and
R4ag, R539, R639, R10ag, R1139, R12ag, R13ag, R16a9 and R17ag are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-io-cycloalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and CiMo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C wherein there may optionally be a covalent bond between the substituents R5ag and R6a9; and
R739 is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, cyano, nitro, Ci-s-alkyi, CW alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sul-

fanyl, sulfo, c1-c6-alkyl, C2-6-alkenyl, arylt heteroaryl, c1-c6-nexerocyuyi optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-^-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!. C2-e-alkenyIl aryl, heteroaryl, C3-8-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Cs-io-cyoloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl( aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, c3-c10cycloalkyi, perhalomethyl and perhalomethoxy;
R8*9, R9as, R14a9 and R15a9 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyi, C2.e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d^-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl, Cs-io-cycloalkyi, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyf, aryl, heteroaryl, C3-s-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, C2_6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-i0-cycloa!kyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-

alkyl, C2-6-alkenyl, heteroaryl, C3-8-heterocyclyl, C3-io-cycloalky[, perhalomethyl and perha-lomethoxy; and
wherein there may optionally be a covalent bond between the substituents R9as and R10as; and
wherein there may optionally be a covalent bond between the substituents R12a9 and R16a9.
210. The compound according to claim 209, wherein there is a covalent bond between the
substituents R5ag and R639.
211. The compound according to any one of claims 209-210, wherein there is a covalent
bond between the substituents R9a9 and R10a9.
212. The compound according to any one of claims 209-211, wherein at least one of RBa9,
R9a9j plOag^ ^^ R12a9j Ria* R14ag an(j R15ag afe se)ected from F> C[i Q^-alkyl, C-^-alkOXy, -
C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and perhalomethyl.
213. A compound of the general formula

wherein R4^, R5ah, R6ah, R7ah, R8ah and R9ah are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-to-cycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aikenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, C2„6-

alkenyl, aryl, heteroaryl, C3_6-heterocycIyl, and c1-c610-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, CWalkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2_e-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, Cs-io-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R53*1 and R6ah are not both CF3; and
wherein there may optionally be a covalent bond between any of the substituents selected from R4*, R5ah, R6ah and R7ah; and
wherein there may optionally be a covalent bond between the substituents R8ah and R9ah; with the proviso that when R8ah and R9ah together with the carbon to which they are bound forms phenyl then R5ahf R6ah, R7ah and R8ah are not all hydrogen.
214. The compound according to claim 213, wherein there is a covalent bond between R8ah and R9ah.
215.. The compound according to any one of claims 213-214, wherein there is a covalent bond between R6ah and R7ah.
216 . The compound according to any one of claims 213-215, wherein there is a covalent bond between R5ah and R6a217. The compound according to any one of claims 223-226, wherein at least one of R5ah, R6ah, R7ah and R8ah are selected from F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
218. A compound of the general formula


R4ai, R**\ R6ai( R7ai, R8ai and R9ai are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and C3-i0-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6s-heterocyciyl, and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, CM-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c1-c6io-cycloalkyl, wherein each of the. hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and ^o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, C2.e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and per-halomethoxy, with the proviso that R4ai is not CHrN(Me)2; and
wherein there may optionally be a covalent bond between any of the substituents selected from R4ai, R5ai, R6ai and R7ai; and

wherein there may optionally be a covalent bond between the substituents RBai and R9ai; with the proviso that R8*1 and R931 together with the carbon to which they are bound do not form 4-methoxy-phenyl, 4-chloro-phenyl or.4-nitro-phenyl.
219. The compound according to claim 218, wherein there is a covalent bond between R8aj and R93'.
220. The compound according to any one of claims 218-219, wherein there is a covalent bond between R631 and R7ai.
221. The compound according to any one of claims 218-220, wherein there is a covalent bond between R5al and R6a'.
222.: The compound according to any one of claims 218-221, wherein at least one of R5ai, R6aif R7ai and R831 are selected from F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
223. A compound of the general formula

wherein R4aj, R5aif R6ai and R7aj are independently selected from amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aIkenylf aryl, heteroaryl, C3-s-heterocyclyl, and Qj-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6 alkyl, C2-6-alkenyl, aryl, heteroaryl, Qj-B-heterocyclyl, and Cs.io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, Qwrheterocyclyl, Cs-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkenyl,

aryl, heteroaryl, c1-c6-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CsMcrcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Gt-6-alkyI, C2^-alkenyl, aryl, heteroaryl, Qj-B-heterocyclyl, CsMo-cycloalkyl, perhalomethyl and perhaiomethoxy; and
wherein there may optionally be a covalent bond between the substituents R4* and R5ai; and
wherein there may optionally be a covalent bond between the substituents R6- and R7aj.
224. The compound according to claim 223, wherein there is a covalent bond between R6aj and R7aj.
225. The compound according to claim 224, wherein R6aj, R7aj and said covalent bond are selected so as to form a ring system selected from an optionally substituted piperedine, piperazine, morpholine and thiomorpholine.
226. The compound according to claim 225, wherein said ring system is selected from piperedine, piperazine, morpholine and thiomorpholine
227. The compound according to any one of claims 223-226, wherein there, is a covalent bond between R4aj and R5aj,
228. A compound of the general formula


wherein R4*, R5ak, R8* and R7ak are independently selected from amino, cyano, nitro, c1-c6-alkyl, C2.e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Ca-i0-cycloalkyl, wherein each of amino, c1-c6-alkyl, C2^-aikenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, c1-c6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and c1-c6io-cycioalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs^-heterocyclyl, and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyi, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloa1kyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, C2^-alkenyi, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs.i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aikenylf aryl, heteroaryl, C3^-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that none of R4akand R5ak are -C(=0)-0-isopropyl; and
wherein there may optionally be a covalent bond between the substituents R43* and R5ak; with the proviso that R43*, R531* and the nitrogen to which they are bound do not form a substituted tetrazolyl moiety; and
wherein there, may optionally be a covalent bond between the substituents Reak and R7ak;
229. The compound according to claim 228, wherein there is a covalent bond between R6ak and R7ak.
230. The compound according to claim 229, wherein R6a\ R7ak and said covalent bond are selected so as to form a ring system selected from an optionally substituted piperedine, piperazine, morpholine and thiomorpholine.
231. The compound according to claim 230, wherein said ring system is selected from piperedine, piperazine, morpholine and thiomorpholine

232. The compound according to any one of claims 228-231, wherein there is a covalent bond between R43* and R**.
233. A compound of the general formula

wherein R481 and R5aI are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyctyl and C3-io-cycloaIkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2.a-alkenyl, aryl, heteroaryl, C3-B-heterocyclyl, and Cs-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ct^-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3_10-cycloalkyi may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aIkenyl, aryl, heteroaryl, C3.s-heterocyclyI, C&.1Crcycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alky!, C2.e-alkenyl, aryl, heteroaryl, C3-B-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-alkyl, c1-c6-alkenyl, aryl, heteroaryl, Cs^-heterocyclyl and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, C2-6-aIkenyl, aryl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between R43' and R5aI; with the proviso that R43* and R5al together with the nitrogen to which they are bound do not form 2,5-pyrrolidinedione or an annealed ring system comprising 3 or more rings; and

wherein E is selected from the group consisting of -0-, -S-, -S(=0)-, «S(=0)2- and -NR14aI-, -CR15a,R16aIs and
Rea R7* Reaf R9d Rioa R«* Ri* R«^ R14* RiM and RiBa» are independently selected
from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and C3.10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Quo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkenyl; aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, d-e-alkyl, C2^-alkenyl, aryl, heteroaryl, C3_s-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CWalkyl, C2_6-aIkenyl, aryl, heteroaryl, C3-5-heterocyclyl, C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-«ncycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Chalky!, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alky!, c1-c6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3.1(rcycloalkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, Qj-io-cyctaalkyl, perhalomethyl and perhalomethoxy; and
wherein there may optionally be a covalent bond between the substituents R7al and Rtol; and
wherein there may optionally be a covalent bond between the substituents R10al and a sub-stituent selected from R14ai and R15aL
234. The compound according to claim 233, wherein there is a covalent bond between the substituents R431 and R5ai.

235. The compound according to any one of claims 233-234, wherein there is a covalent
bond between the substituents R7al and R8al.
236. The compound according to any one of claims 233-235, wherein there is a covalent
bond between R10al and a substituent selected from R14aI or R15al.
237. The compound according to any one of claims 233-235, wherein E is -NR14a'-.
238. The compound according to claim 237, wherein R14aI is selected from F, CI, d-e-alkyl,
c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)rOH, hydroxy, amino and
perftalomethyl.
239. The compound according to any one of claims 233-235, wherein E is -CR15alR16a1-.
240. The compound according to claim 239, wherein R16al is selected from F, CI, c1-c6-alkyl,
c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and
perhalomethyl.
241. The compound according to any one of claims 239-240, wherein R15al is hydrogen.
242. The compound according to any one of claims 233-241, wherein at least one of R6al, R7a\ R8al, R9al, R10al, R11aIf R12al and R13aI are selected from F, CI, c1-c6-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH,-S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
243. A compound of the general formula

wherein E is selected from the group consisting of-0-, -S-, -S(=0)-, -S(=0)2- and -NR14am-,

-CR15amR16am~; and
wherein A1am is N or C-R17am; A23"1 is N or C-R18am; A331" is N or C-R19am; A43"1 is N or OR20""1; and
p6am p7am p8am pQam p10am p11am p12am p13am pt4am p15am p16am p17am p18am p19am «nf4
R20am are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1_6-alkyl, C2^-alkenyl, aryi, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6nrcydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, C2.B-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloaIkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocycIyI, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and c1-c610-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, c1-c6-alkenyl, aryl, het-: eroaryl, c1-c6-heterocyclyl and C3-io-cycIoalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl,. C2_6-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl, and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6e-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, c3-c10cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R17am and R203™ are not both hydroxy; and
wherein there may optionally be a covalent bond between R18am and a substituent selected from R17am and R19am; and
wherein there may optionally be a covalent bond between the substituents R10am and a substituent selected from R14am and R15am; and

wherein there may optionally be a covalent bond between the substituents R7am and R8am.
244. The compound according to claim 243, wherein there is a covalent bond between R1Bam and a substituents selected from R17am and R19am.
245. The compound according to any one of claims 243-244, wherein there is a covalent bond between R10am and a substituent selected from R14am or R15am.
246. The compound according to claim 243, and , wherein E is -NR14am-.
247. The compound according to claim 246, wherein R14am is selected from F, CI, c1-c6-alkyl, c1-c6e-alkoxy, -C(=0)NH2, -NHC(=0)-OH? -S(=0)2-NH2| -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
248. The compound according to claim 243, wherein E is -CR15amR16am-.
249. The compound according to claim 248, wherein R16am is selected from F, CI, d-e-alkyl, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
250. The compound according to any one of claims 248-249, wherein R15am is hydrogen.
251. The compoud according to claim 248, wherein there is a covalent bond between R15am and R16am.
252. The compound according to any one of claims 243-251, wherein at least one of R6am,
pTam^ R6am( R9am( plOarr^ pllar^ R12am and R13am gre se|ected from Fj Q|f c1-c6-alkyl, c1-c6-alkOXy,
-C(=0)NH2f -NHC(=O)-0H, -S(=0)2-NH2, -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
253. A compound of the general formula


wherein E is selected from the group consisting of -0-, -S-, S(rO)~, -S(=0)r and -NR17an-, -CR18anR19an-; and
p4an p5an p6an p7an p8an p9an p10an p11an p12an pl3an nUan p15an p16an p17an p18an anf4
R19an are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci-e-alkyI, Cz^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, Ca-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaIkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Chalky!, C2-e-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and Cs-io-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6alkyl, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, Ca-s-heterocyclyl, C3-io-cycloalkyl, wherein each of the hydroxy, sulfanyl,. amino, sulfo, Ct-e-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci_6-alkyl, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and Q^o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, c1-c6alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl and c3-c10cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3^-heterocyclyl, and c3-c10cycioalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cve-alkyl, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, C3-io-cycloalkyl, perhalomethyl and perhalomethoxy; with the proviso that R43" is
not methyl or phenyl; and
i

wherein there may optionally be a covalent bond between RiaBn and a substituent seiectea from R17an and R1&an; and
wherein there may optionally be a covalent bond between the substituents R7an and RBan.
254. The compound according to claim 253, wherein R48" is a substituted heteroaryl.
255. The compound according to claim 254, wherein said substituted heteroaryl is a substituted pyridine.
256. The compound according to any one of claims 253-255, wherein there is a covalent bond between the substituents R7an and R830.
257. The compound according to any one of claims 253-256, wherein there is a covalent bond between R13an and a substituents selected from R17an and R1Ban.
258. The compound according to any one of claims 253-256, wherein E is -NR17an-.
259. The compound according to any one of claims 253-256, wherein E is -CRlBanR19an-.
260. The compound according to claim 259, wherein R19an is selected from F, CI, c1-c6-alkyl, c1-c6alkoxy, -C(=0)NH2) -NHC(=0)-OH, -S(=0)2-NH2, -NH^S(=0)rOH, hydroxy, amino and perhalomethyl.
261. The compound according to any one of claims 259-260, wherein R18an is hydrogen.
262. The compound according to any one of claims 253-261, wherein at least one of R5an, R6an, R7an, R8an, R9an, R10an, R11an, R12an, R13an, R14an, R15an and R16an are selected from F, CI, c1-c6-alkyl, Ci-e-aikoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=OVNH2l -NH-S(=0)2-OH, hydroxy, amino and perhalomethyl.
263. A compound of the general formula


wherein R4ao is selected from hydrogen, hydroxy, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and d-io-cycloalkyl, wherein each of hydroxy, sulfo, amino, d-e-alkyl, d.«-alkenyl, aryl, heteroaryl, d-e-heterocyclyl and d-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkenyl,. aryl, heteroaryl, d-s-heterocyclyl and d-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl* d-e-alkenyl, aryl, heteroaryl, d-e-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, d-e-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, d-s-alkenyl, aryl, heteroaryl, d-s-heterocyclyl and d-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, d-s-heterocyclyl and d_10-cycloalkyl roay optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, d-e-heterocyclyl and d. to-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-s-alkyl. d-6-alkenyi, aryl, heteroaryl, c1-c6-heterocyclyl and C3.i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, d^-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R5ao, RBao, R7a0, R8ao, R9ao, R10ao, R11ao and R12ao are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, d^-heterocyclyl, and d-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, d-s-alkenyl, aryl, heteroaryl, d^rheterocyclyl and d-to-cycloalkyl rnay optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, d-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and d-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-s-alkyl,

C2-6-a!kenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6alkyl, C2.6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, CWalkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-alkenyI, aryl, heteroaryl, C3-8-heterocyclyl and C3-icrcycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-beterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-icrcycloalkyI, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-a!kenyl, perhalomethyl and perhalomethoxy;
with the proviso that any one of R6ao and R8ao is not methyl; and with the further proviso that R430, R530, R6ao, R7ao and R890 are not all hydrogen; and
wherein there may optionally be a covalent bond beween R430 and R6a0; and wherein there may optionally be a covalent bond between R7ao and R8ao; and wherein there may optionally be. a covalent bond between R9ao and R10ao.
264. The compound according to claim 263, wherein R5a0, R6ao, R7ao and R8ao are independently selected from hydrogen and fluor.
265. The compound according to any one of claims 263-264, wherein R9ao, R10ao, R11a0 and R12ao are independently selected from hydrogen and fluor.
266. A compound of the general formula


wherein R1ap and R23*5 are independently selected from Cnj-alkyl, C2^-aIkenyI, aryl, heteroaryl, CWheterocyclyl, and C3-io-cycloalkyl, herein each of Chalky!, C2_6-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl, C2^alkenyl, aryl, heteroaryl, C3.B-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, nitro, c1-c6-alkyl, C2„ralkenyl, aryl, heteroaryl, C3-8-heterocyc!yl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, CW-heterocycIyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2.6-alkenyi, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, perhalomethyl and perhalomethoxy; with the proviso that if R1ap and R28* are identical then they are not methyl or ethyl; and
wherein there may optionally be a covalent bond between the substituents R1ap and R23*3; and
wherein R5ap, R6ap and R7ap are independently selected from hydrogen and F; and

wherein R4^ is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, d^-alky!, C2^alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl, and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalky!, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, Q^-heterocyclyl and C3. 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, Cs-e-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6icrcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6~alkenyl, aryl, heteroaryl, Qj-a-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, Ca-e-alkenyl, perhalomethyl and perhalomethoxy; with the proviso that R4^ is not methyl.
267. The compound according to claim 266, wherein R1ap and R2ap are not identical.
268. A compound of the general formula


wherein R1aq and R2** are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-oycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, C2.5-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and C3-io-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C«-alkyl, (Walkenyi, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci_6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6s-heterocyclyl and C3. io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, C2_6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3_io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, c1-c6alkenyl, perha-lomethyl and perhalomethoxy; with the proviso that R1aq and R23" are not both methyl; and
wherein there may optionally be a covalent bond between R1aq and R2^; and

wherein R4aq, R5aq, R6aq, R7aq, R8aq, R9aq, R10aq and R11ao are indenpendently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6alkyl, c1-c6-alkenyl, aryl, heteroaryl, Q^rheterocyclyl, and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocydyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ct-e-alkyI, C2.6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyi, aryl, heteroaryl, Cwrheterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C-^-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-6-heterocyc!yl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycioalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl. C2-e-alkenyl, aryl, heteroaryl, c1-c6r heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2.6-alkenyl, aryl, heteroaryl, C3_g-heterocycIyl and C3-«rcycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3. 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-aIkenyl,
perhalomethyl and perhalomethoxy; and
1
wherein there may optionally be a covalent bond between R4*1. and R5aq; and
wherein R3aq is selected from the group consisting of-C(=0)-, -C(=0)NH-, -CH2-, -CH2CH2-, -CHF-, «CH2CHF-, -CHFCHr, -NH-, -S(=0)2-NH-, -NH-S(=0)r, -NHC(=0)-, -0-, -S-, -S(=0> . -S(=0)2-; and
wherein there may optionally be a covalent bond between two substituents selected from R**, R9aq, R10aq and R11a0.
269. The compound according to claim 268, wherein there is one covalent bond between the substituents R1aq and R2^.
1

270. The compound according to any one of claims 268-269, wherein R4^, R5aq, R6aq and R7aq are independently selected from hydrogen and fluor.
271. The compound according to any one of claims 268-270, wherein R3^ is selected from -0-, -S-, -CHr, -CH2CHr, -NH-, -NH-C(=0)-, -C(=0)-NH-( -S(=0)2-NH- and -NH~S(=0)2-.
272. A compound of the general formula

wherein A1ar is N or C-R10ar; and A2* is N or C-R11ar; and A3ar is N or C-R12ar; and
wherein R1ar, R23', R3ar, R48', R5ar, R6ar, R7ar, R8ar, R93', R10ar, R11ar and R12ar are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2. e-alkenyl, aryl, heteroaryl, c1-c68-heterocyclyl, and C3-io-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, c1-c6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, (^-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cn^-alkyl, Ca^-alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyt, C2-e-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo,

halogen, amino, cyano, nitro, Chalky!, (Walkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3. 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-aIkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and c1-c6io-cycloalkyl may optionally be substituted with one or more, substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alky!, CWalkenyl, perhalomethyl and perhalomethoxy; with the proviso that if R1ar and R231" are identical then they are not methyl or ethyl; and
wherein there may optionally be a covalent bond between R1ar and R23*".
273. The compound according to claim 272, wherein R9ar is S(=0)2-R13ar or C(=0)-R13ar; and wherein R13ar is selected from hydroxy, sulfanyl, sulfo, amino, Chalky!, C2-6-aIkenylf aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci-e-alkyI, C2^-a!kenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Qj-s-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-aikyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl* sulfo, amino, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c1-c6trcycioaikyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2.6-alkenyl, perhalomethyl and perhalomethoxy
274. The compound according to any one of claims 272-273, wherein R1ar and R291" are not identical.
275. The compound according to any one of claims 272-274, wherein there is a covalent bond between the substituents R1ar and R231".
276. A compound of the general formula


wherein R1as, R285, R383, R4as, R5as, R6as, R7as, R8as and R938 are independetly selected from hydrogen and fluon and
wherein R10as is selected from aryl and heteroaryl, which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cydoalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalky!, Cs-e-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and CsMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-aIkenyl, aryl, heteroaryl, C3^heterocyclyl and C3-1Crcycloalkyl may optionally be substituted with one. or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-aikyl, c1-c6-alkenyi, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Qs-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1^-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6»alkenyl, aryl, heteroaryl, c1-c6rheterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalky!, C2-e-aIkenyl, perhalomethyl and perhalomethoxy; and
wherein R12as is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, cyano, c1-c6-alkyl, C2. e-alkenylr aryl, heteroaryl, c1-c6heterocyclyl, and C3_10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyi, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyi, C2^-alkenyl,

aryl, heteroaryl, CM-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxof halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3-i0-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and CsMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^alkenyl, aryl, heteroaryl, C3-8-heterocyciyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-alkenyl, aryl, heteroaryl, C3-e-heterocyclyl and CsMo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, c1-c6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R13as, R14as, R15as and R16as are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocycIyl and c3-c10cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-a-heterocyclyl and c1-c6 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6alkyl, C2^-alkenyl, aryl, heteroaryl, C3_e-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2^-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d-e-alkyl, C2_6-alkenyI, aryl, heteroaryl, c1-c6-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Chalky!. C2.6-alkenyl, aryl, heteroaryl, Cs-8-heterocyclyl and C3-io-cycloaIkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, c1-c6-aikenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C$. 1crcycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e-alkyI, C2^-alkenyl, aryl, heteroaryl, C3_s-heterocyclyl and C3-io-cycioaIkyl, wherein each of hydroxy, sulfanyl,

ilfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl ay optionally be substituted with one or more substituents independently selected from hy-oxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, perha-methyl and perhalomethoxy; with the proviso that Rt2as, R13as, R14as, R15as and R16as are not I hydrogen; and
herein there may optionally be a covalent bond between the substituents R13as and R14as.
77. The compound according to claim 276, wherein R13as, R14as, R15as and R16as are inde-
endently selected from hydrogen and fluor.
78. A compound of the general formula

wherein R5*, R6at, R7at R8al, R9at, R10at R11at, R12a\ R13at R14at, R15at, R16at, R17al and R18al are independently selected from hydrogen and fluor, and
wherein R4at is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci_6-alkyl, C2.6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3.10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, d^-alkyl, C2_6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, Q^e-alkeny!, aryl, heteroaryl, c1-c6-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyt, aryl, heteroaryl, c1-c6-heterocyclyl and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, het-

eroaryl, C-^-heterocydyl and Gs-io-cycloalkyi, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alky!, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl may op* tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfb, oxo, halogen, amino, cyano, nitro, d-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6a-heterocyclyl and C3-to-cycloalkyl( wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nrtro, c1-c6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy; and
wherein R19at is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, C% e-alkyl, c1-c6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl, and CMo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and Quo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-6-alkyl, C2-e-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and c3-c10 cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2_6-alkenyl, aryl, heteroaryl, C«-heterocyclyl and C3.io-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2-6-alkenyl, aryl, heteroaryl, c1-c6-heterocyclyl and C3-io-cycloaikyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, c1-c6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-s-heterocyclyl and c3-c10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, c1-c6-alkyl, C2^-alkenyI, aryl, heteroaryl, C3-B-heterocyclyl and C3-10-cycloaIkyI may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, fluor, iodine, amino, cyano, nitro, c1-c6-alkyl, C2-e-aIkenyl, aryl, heteroaryl, C3-8-heterocycly! and C3-io-cycloalkyl; with the proviso that R19at is not methoxy.
279. The compound according to claim 278, wherein R5a\ R6*, R7at R8al, R9at, R10at R11at, R12at,
R13at R14* R1S* R1M R17at and R18at ape aj( hydrogen.
280. The compound according to any one of claims 278-279, wherein R4at is an optionally
substituted aryl or heteroaryl.

281. The compound according to any one of claims 1-280, wherein said compound com
prises only one F.
282. The compound according to any one of claims 1-280, wherein said compound com
prises two F and preferably three F.
283. The compound according to any one of claims 1-280, wherein said compound com
prises a CF3 moiety.
284. The compound according to any one of claims 1-283, wherein said compound comprises a hydrophilic substituent selected from the group consisting of hydroxy, amino, c1-c6-alkoxy, -C(=0)NH2, -NHC(=0)-OH, -S(=0)2-NH2, -NHS(=0)2-OH, -NHC(=0)-R1am, -NHS(=0)2-R1an\ -N(R1am)C(=0)-R2am, -N(R1am)S(=0)2-R2aml wherein R1am and R2"" are independently selected from Chalky!.
285. The compound according to any one of claims 1-283, wherein said compound comprises a moiety selected from the group consisting of
£




































2H), 2.63 (t, 2H), 2.12 (qu, 2H).
Example 176 (General procedure 1) Methyl-phenyl-carbamic acid benzo[d]isoxazoI-3-yl ester
The title product was prepared from benzo[d]isoxazol-3-ol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (53%, colorless oil). HPLC-MS: mtz= 291.1 (M+23); Rt: 4.05 min.
1H NMR (CDCIs): 7.60-7.75 (m, 1H), 7.49-7.60 (m, 2H), 7.38-7.48 (m, 4H)i 7.28-7.36 (m, 2H), 3.46 (sf 3H).
Example 177 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-2-yI ester
The title product was prepared from 2-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (57%, colorless oil). HPLC-MS: m/z= 229.1 (M+23); Rt: 2.80 min.
1H NMR (CDCI3): 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7.45 (m, 4H), 7.22-7.34 (m, 1H), 7.14-7.21 (t, 1H), 6.99-7.15 (bs, 1H), 3.44 (s, 3H).
Example 178 (General procedure 1)
Methyl-phenyl-carbamic acid 1-(methyl-phenyl-carbamoyl)-1H-benzimidazol-2-yl ester
The title product was prepared from 2-hydroxybenzimidazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (14%, white crystals). HPLC-MS: m/z= 401.2 (M+1); Rt: 3.88 min, purity: 83%. 1H NMR (CDCI3): 7.32 (dd, 2H), 7.24-7.28 (m, 2H), 7.21-7.24 (m, 2H), 7.29 (t, 1H), 7.12-7.19 (mf 5H), 7.09-7.15 m, 2H), 3.28 (s, 6H).
Example 179 (General procedure 1)
Methyl-phenyl-carbamic acid 4-[(pyridine-3-carbonyI)-amino]-phenyl ester
The title product was prepared from N-(4-Hydroxy-phenyl)-nicotinamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (1%, light yellow crystals). HPLC-MS: m/z= 348.1 (M+1); R<: min.>
Example 180 (General procedure 11)
4-Py!ToIidin-1-yl-piperidine«1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4«(5-trifluoromethy!-pyridin}-2-yloxy)-phenoI and 4-(1-pyrrolidinyI)piperidine. The crude product was used without further purification (68%, white solid). HPLC-MS: rnlz = 436.2 (M+1); Rt: 2.98 min. 1H NMR (DMSO-d6): 10.90 (bs, 1H), 8.57 (s, 1H), 8.24 (dd, 1H), 7.15-7.30 (m, 5H), 4.00-
4.40 (m, 2H), 3.45-3.60 (m, 2H), 2.75-3.25 (m, 4H), 2.05-2.25 (d, 2H), 1.80-2.05 (m, 5H),
1.60-1.80 (m,2H).
Example 181 (General procedure 12)
Methyl-o-tolyl-carbamic acid 4-(trifluoromethyI-pyridin-2-yioxy)-phenyI ester
The title product was prepared from 4-(5-trifluoromethyI-pyridin)»2-yloxy)-phenoI and N-methyl-o-toluidine. The crude product was subjected to preparative HPLC (51%, colorless oil). HPLC-MS: mlz = 403.2 (M+1); Rt: 4.89 min.
1H NMR (CDCI3): 8.40 (s, 1H), 7.87 (dd, 1H), 7.05-7.18 (m, 4H), 6.96 (d, 1H), 3.30 (s, 3H), 2.36 (s, 3H).
Example 182 (General procedure 12)
Methyl-pyridin-2-yl-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 2-(methylamino)pyridine. The crude product was subjected to preparative HPLC (55%, white solid). HPLC-MS: rnlz =390.1 (M+1); Rt: 4.31 min.
Example 183 (General procedure 12)
Methyl-m-tolyl-carbamic add 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5«trifluoromethyl-pyridin)-2-yloxy)-phenol and N-methyl-m-toluidine. The crude product was subjected to preparative HPLC (51%, colorless oil). HPLC-MS: rnlz = 403.2 (M+1); Rt: 4.98 min. 1H NMR (CDCI3): 8.42 (s, 1H), 7.88 (dd, 1H), 7.28 (d, 1H), 7.05-7.25 (m, 7H), 6.97 (d, 1H),
3.41 (sf 3H), 2.38 (s, 3H).

Example 184 (General procedure 12)
(3-ChIoro-phenyI)-methyI-carbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yioxy)-phenoI and 3-chloro-N-methyianiline. The crude product was subjected to preparative HPLC (54%, colorless oil). HPLC-MS: mlz = 423.1 (M+1); R{: 5.07 min.
1H NMR (CDCI3): 8.42 (m, 1H), 7.88 (dd, 1H), 7.39 (m( 1H), 7.33 (t, 1H), 7.22-7.30 (m, 2H), 7.10-7.7.22 (m, 4H), 6.99 (d, 1H), 3.43 (s, 3H).
Example 185 (General procedure 12)
Methyl-p-tolyi-carbamic acid 4-(5-trifluoromethyl -pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and N-methyl-p-toluidine. The crude product was subjected to preparative HPLC (54%, white solid). HPLC-MS: m/z= 403.2 (M+1); Rt: 4.99 min.
1H NMR (CDCI3): 8.42 (s, 1H), 7.87 (dd, 1H), 7.05-7.30 (m, 8H), 6.98 (d, 1H), 3.40 (s, 3H)f 2.36 (s, 3H).
Example 186 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(3-pyridin-3-yl-acryloyl)-phenyl ester
The title product was prepared from 1-(4-hydroxy-phenyI)-3-pyridin-3-yl-prop-2-en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (56%, off-white solid). HPLC-MS: mlz = 359.0 (M+1); Rt: 3.27 min. 1H NMR (CDCI3): 8.87 (d, 1H), 8.65 (dd, 1H), 8.03 (d, 2H), 7.97 (dt, 1H), 7.79 (d, 1H), 7.57 (d, 1H), 7.33-7.47 (m, 5H), 7.27-7.33 (m, 3H), 3.44 (s, 3H), 3.49 (t, 1H), 1.21 (t, 1H).
Example 187 (General procedure 14)
Methyl-phenyl-carbamic add 4-[3-(3I4!5-trimethoxy-phenyl)-acryloyl]-phenyl ester
The title product was prepared from 1-(4-hydroxyphenyl)-3-(3,4,5-trimethoxyphenyI)prop-2-en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (82%, yellow solid). HPLC-MS: mlz = 448.2 (M+1); Rt: 4.61 min. 1H NMR (CDCU): 8.01 (d, 2H), 7.70 (d, 1H), 7.33-7.47 (m, 4H), 7.28-7.33 (m, 2H), 6.86 (s,

IH), 3.92 (s, 6H), 3.90 (s, 3H), 3.45 (s, 3H).
Example 188 (General procedure 14)
Methyl-phenyl-carbamic acid 4-diethylcarbamoyl-2-methoxy-phenyl ester
The title product was prepared from N,N-diethyI-4-hydroxy-3-methoxy-benzamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (58%, colorless oil). HPLC-MS: mlz= 357.1 (M+1); Rt: 3.64 min.
1H NMR (CDCI3): 7.34-7.44 (m, 4H), 7.21-7.28 (m, 1H), 7.03-7.09 (d, 1H), 6.99 (d, 1H), 6.90 (dd, 1H)f 3.87 (s, 3H), 3.15-3.65 (bs, 4H), 3.43 (s, 3H), 1.05-1.35 (m, 6H).
Example 189 (General procedure 14) Methyl-phenyl-carbamic acid 3-phenylcarbamoyi-phenyl ester
The title product was prepared from 3-hydroxy-N-phenyl-benzamide and N-methyl-N-
phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (54%,
white solid). HPLC-MS: m/z= 347.2 (M+1); Rt: 4.01 min.
1H NMR (CDCl3): 7.76 (s, 1H), 7.68 (d, 1H), 7.58-7.65 (m, 3H), 7.27-7.51 (m, 8H), 7.15 (t,
1H),3.44(s,3H).
Example 190 (General procedure 14) Methyl-phenyl-carbamic acid quinolin-7-yl ester
The title product was prepared from 7-hydroxyquinoline and N-methyi-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (28%, white solid). HPLC-MS: m/z= 279.1 (M+1); R*: 2.55 min.
1H NMR (CDCI3): 8.93 (dd, 1H), 8.18 (d, 1H), 7.83-7.86 (m, 1H), 7,82 (d, 1H), 7.35-7.50 (m, 6H), 7.27-7.32 (m, 1H)r 3.47 (s, 1H).
Example 191 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(4-methyl-piperazine-1-carbonyl)-phenyl ester
The title product was prepared from 1-(4-hydroxybenzoyl)-4-methyl-piperazine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (22%, colorless oil). HPLC-MS: m/z = 354.1 (M+1); Rt: 2.07 min.

1H NMR (CDCI3): 7.37-7.49 (m, 4H), 7.28-7.37 (m, 3H), 7.16-7.25 (m, 2H), 4.60-4.00 (bs( 2H), 3.43 (s, 3H), 3.35-3.90 (bs, 4H), 2.82 (s, 3H) 2.55-2.90 (bs, 2H).
Example 192 (General procedure 14) Methyl-phenyi-carbamic acid 3-acetylamino-phenyI ester
The title product was prepared from 3-acetamidophenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (66%, white solid). HPLC-MS: m/z= 285.1 (M+1); Rt: 3.09 min.
1H NMR (CDC!3): 7.40-7.49 (m, 1H), 7.31-7.40 (m, 5H), 7.25-7.30 (m, 1H), 7.22 (d, 1H), 7.14 (d, 1H)f 6-84 (bd, 1H), 3.42 (s, 3H), 2.10 (s, 3H).
Example 193 (General procedure 14) Methyl-phenyi-carbamic acid 4-benzoyI-phenyI ester
The title product was prepared from (4-hydroxy-phenyI)-phenyI-methanone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (36%, colorless oil). HPLC-MS: m/z = 332.2 (M+1); Rt: 4.42 min.
1H NMR (CDCI3): 7.75-7.85 (m, 4H), 7.58 (tt, 1H), 7.33-7.52 (m, 6H), 7.27-7.32 (m, 1H), 7.18-7.25 (m, 2H), 3.44 (s, 3H).
Example 194 (General procedure 14) Methyl-phenyi-carbamic acid biphenyl-3-yl ester
The title product was prepared from 3-phenyiphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (52%, colorless oil). HPLC-MS: mtz = 304.2 (M+1); Rt: 4.75 min. 1H NMR (CDCI3): 7.52-7.67 (m, 2H), 7.22-7.52 (m, 11H), 7.03-7.22 (m, 1H), 3.45 (s, 3H).
Example 195 (General procedure 14) Methyl-phenyi-carbamic add 1H-indol-4-yl ester
The title product was prepared from 4-hydroxyindole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (48%T off-white solid). HPLC-MS; m/z = 267.1 (M+1); Rt: 3.57 min.

1H NMR (CDC!3): 8.20 (els, 1H), 7.36-7.50 (m, 4H), 7.17-7.35 (m, 2H), 7.08-7.17 (m, 2H), 6.94 (d, 1H), 6.44 (s, 1H), 3.48 (s, 3H).
Example 196 (General procedure 14)
Methyl-phenyl-carbamic acid 5,6,7,8-tetrahydro-naphthalen-1-yI ester
The title product was prepared from 5,6,7,8-tetrahydro-1-naphthol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (42%, colorless oil). HPLC-MS: m/z= 282.1 (M+1); Rt: 4.77 min.
1H NMR (CDCI3): 7.33-7.45 (m, 4H), 7.22-7.32 (m, 1H), 7.02-7.13 (t, 1H), 6.82-7.96 (m, 2H), 3.42 (s, 3H), 2.70-2.82 (m, 2H), 2.50-2.65 (m, 2H), 1.62-1.83 (m, 4H).
Example 197 (General procedure 14)
Methyl-phenyl-carbamic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-1-y] ester
The title product was prepared from 5,6J,8-tetrahydro-1-naphthoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (60%, colorless oil). HPLC-MS: m/z= 296.1 (M+1); Rt: 3.81 min.
1H NMR (CDCI3): 7.91 (dd, 1H), 7.21-7.50 (m, 7H), 3.44 (s, 3H), 2.60-2.93 (bs, 2H), 2.62 (t, 2H), 2.02-2.20 (m, 2H).
Example 198 (General procedure 14)
Methyl-phenyl-carbamic acid 1,3-dioxo-1,3-dihydro-isobenzofuran-4-yi ester
The title product was prepared from 4-hydroxy-isobenzofuran-1,3-dione and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: ro/z= 298.1 (M+1); Rt: 2.58 min, purity: 85%. 1H NMR (CDCI3): 7.90 (d, 1H), 7.48-7.62 (m, 2H), 7.28-7.45 (m, 5H), 3.38 (s, 3H).
Example 199 (General procedure 1)
Methyl-phenyl-carbamic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-chloro-pyridin-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to column chromatography (ethyl acetate/heptane (1:5) (85%, white solid). HPLC-MS: mJz= 355.1 (M+1); R*: 4.56 min.

1H NMR (CDCI3): 8.10 (df 1H), 7.62 (dd, 1H), 7.31-7.44 (m, 4H), 7.25-7.30 (m, 1H), 7.05-7.20 (m, 4H), 6.84 (d, 1H), 3.43 (s, 3H).
Example 200 (General procedure. 14)
(3-Fluoro-pheny()-methyl-carbamic acid 4-(5-tnTIuoromethyl-pyridin-2-yIoxy)-phenyl ester
The title product was prepared from 4-(5"TrifIuoromethyI-pyridin-2-yloxy)-phenoI and 3-fluoro-N-methylaniline. The crude product was subjected to preparative HPLC (31%, white solid). HPLC-MS: m/z = 407.0 (M+1); Rt: 4.93 min.
1H NMR (CDC!3): 8.42 (s, 1H), 7.88 (dd, 1H), 7.36 (q, 1H), 7.07-7.24 (m, 6H), 7.00 (d, 1H), 7.92-7.05 (rn, 1H), 3.44 (s, 3H).
Example 201 (General procedure 11)
4-Benzy!-piperazine-1-carboxylic acid 4-(5-chloro~pyridin-2-yIoxy)-phenyI ester
The title product was prepared from 4-(5-chIoro-pyridin-2-yIoxy)-phenol and 1-benzylpiperazine. The title product precipitated from the reaction mixture and was collected by filtration (88%, off-white solid). HPLC-MS: rnlz = 424.1 (M+1); Rt: 2.91 min. 1H NMR (CDCI3): 13.86 (bs, 1H)f 8.11 (d, 1H)f 7.60-7.70 (m, 3H), 7.45-7.55 (m, 3H), 7.05-7.20 (m, 4H), 6.98 (d? 1H), 4.26-4.40 (m, 2H, 4.15-4.25 (m, 2H), 3.38-3.53 (m, 2H)f 3.60-4.15 (m, 2H), 2.72-2.92 (m, 2H).
Example 202 (General procedure 11)
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yIoxy)-phenyI ester
The title product was prepared from 4~(5-chloro-pyridin-2-yloxy)-phenoI and (3-pyridylmethyl)piperazine. The title product precipitated from the reaction mixture and was collected by filtration and recrystallized from ethanol (35%, off-white solid). HPLC-MS: mfz = 425.2 (M+1); Rt: 2.39 min.
1H NMR (CDCI3): 13.00-14.50 (bs, 1H), 8.72 (d, 2H)( 8.50 (bs, 1H), 8.11 (d, 1H), 7.64 (dd, 1H), 7.56 (bs, 1H), 7.06-7.14 (m, 4H)f 6.88 (df 1H), 3.6-4.4 (m, 6H), 2.70-3.50 (m, 4H).
Example 203 (General procedure 14)
4-Hydroxymethyl-piperidine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-pheny( ester

The title product was prepared from 4-(5-chloro-pyridin-2-ylaxy)-phenoI and 4-hydroxymethyl-piperidine..The crude product was subjected to column chromatography (ethylacetate/heptane, 1:1) (75%, colorless oil). HPLC-MS: mlz- 363.1 (M+1); Rt: 3.58 min. 1H. NMR (CDCIs): 8.12 (d, 1H), 7.64 (dd, 1H), 7.05-7.24 (m, 4H), 6.85 (d, 1H), 4.33 (ds, 2H), 3.56 (t, 2H), 2.75-3.10 (m, 2H), 1.69-1.95 (m, 3H)f 1.56 (s, 1H), 1.19-1.45 (m, 2H).
Example 204 (General procedure 1) Methyl-phenyl-carbamic acid 4-morpholin-4-yl-phenyl ester
The title product was prepared from and 4-morpholin-4-yI-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was extracted with dichloromethane from citric acid (5%). The combined organic phases were evaporated and the product crystallized from ethanol (22%, crystals). HPLC-MS: m/z= 313.2 (M+1); Rt: 3.75 min.
1H NMR (DMSO-d6): 7.35-7.50 (m, 4H), 7.22-7.32 (m, 1H), 7.00 (d, 2H), 6.92 (d, 2H), 3.72 (t, 4H), 3.32 (s, 3H), 3.05 (t, 4H).
Example 205 (General procedure 1)
1,4-Dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4-piperidone ethylene ketal. The crude product was extracted with dichloromethane from citric acid (5%). The. combined organic phases were evaporated and the product crystallized from ethanol (61 %, crystals). HPLC-MS: mlz = 425.2 (M+1); Rt: 4.45 min.
Example 206 (General procedure 14)
The title product was prepared from 2-(4-hydroxy-phenyl)-indan-1,3-dione and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (1%, oil). HPLC-MS: mlz* 372.1 (M+1); Rt: 4.80 min.
Example 207 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(5,6-dichloro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-phenyI ester
The title product was prepared from 5,6-dichloro-2-(4-hydroxy-phenyI)-isoindole-1,3-dione

and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (2%,). HPLC-MS: m/z = 441.1 (M+1); Rt: 5.00 min.
Example 208 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(2-phenoxy~acetylamino)~phenyI ester
The title product was prepared from N-(4-hydroxy-phenyI)-2-phenoxy-acetamide and N-methyl-N-phenylcarbarnoyl chloride. The crude product was purified by preparative HPLC (54%, oil). HPLC-MS: m/z= 277.2 (M+1); Rt: 4.19 min.
Example 209 (Genera! procedure 14)
Methyl-phenyl-carbamic acid 4-[2-(4-chloro-phenyI)-ethyI]-phenyl ester
The title product was prepared from 4-(4-chlorophenethyI)-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (57%, white crystals). HPLC-MS: m/z= 366.1 (M+1); Rt: 5.58 min.
1H NMR (CDCI3): 7.31-7.45 (m, 4H)( 7.17-7.30 (m, 3H)f 6.96-7.12 (m, 6H), 3.41 (s, 3H), 2.85 (s, 4H).
Example 210 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester
The title product was prepared from pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (41%,)- HPLC-MS: m/z= 348.1 (M+1); Rt: 4.00 min.
1H NMR (CDCI3): 7.32-7.47 (m, 4H), 7.24-7.31 (m, 3H), 7.10-7.23 (m, 4H), 7.79 (d, 2H), 3.41 (m, 6H).
Example 211 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[methyI-(thiophene-2-carbonyl)-amino]-phenyl ester
The title product was prepared from thiophene-2-carboxylic acid (4-hydroxy-phenyI)-methyl-amide and N-methyl-N-phenylcarbamoyI chloride. The crude product was subjected to preparative HPLC (16%, oil). HPLC-MS: mlz = 367.2 (M+1); Rt: 3.97 min.

Example 212 (General procedure 14) Methyl-phenyl-carbamic acid 4-butyrylamino-phenyl ester
The title product was prepared from4'-hydroxybutyraniIide and N-methyl-N-phenylcarbarnoyl chloride. The crude product was subjected to preparative HPLC (60%, white solid). HPLC-MS: mlz = 313.2 (M+1); R*: 3.58 min.
Example 213 (General procedure 14)
Methyl-phenyl-carbamic acid 4-(4,6-dimethyI-pyrimidin-2-yIsulfanyl)-phenyl ester
The title product was prepared from 4-(4,6-dimethyIpyrimidin-2-ylsuIfanyI)-phenoI and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (59%, white solid). HPLC-MS: m/z = 366.1 (M+1); Rt: 4.50 min.
1H NMR (CDCI3): 7.59 (d, 2H), 7.32-7.45 (m, 4H), 7.23-7.31 (m, 1H), 7.16 (d, 2H), 6.68 (s, 1H), 3.43 (s,1H), 2.32.
Example 214 (General procedure 14) Methyl-phenyl-carbamic acid 4-methanesulfonyl-phenyl ester
The title product was prepared from 4-methyIsulfonylphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: mlz = 306.1 (M+1); Rt: 3.22 min.
Example 215 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[2-(3-oxo-1,2,3,4-tetrahydro-quinoxalin-2-yl)-acetylamino]-
phenyl ester
The title product was prepared from N-(4-hydroxyphenyl)-2-(3-oxo-1,2,3,4-tetrahydro-2-quinoxalinyf)acetamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (20%, yellow solid). HPLC-MS: m/z= 431.2 (M+1); Rt: 3.55. min.
Example 216 (General procedure 14) Methyl-phenyl-carbamic acid 4-phenylacetyl-phenyl ester

The title product was prepared from benzyl 4-hydroxyphenyi ketone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (68%, light yellow oil). HPLC-MS: mtz = 431.2 (M+1); Rt: 3.55 min.
Example 217 (General procedure 12)
4-Benzoyl-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yloxy)-phenoI and 4-benzoylpiperidine (29%, white solid). HPLC-MS: m/z= 471.3 (M+1); Rt: 5.12 min.
Example 218 (General procedure 11)
[1,4]BipiperidinyI-1'-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-trifluoromethyl-pyridin)-2-yIoxy)-phenoI and 4-piperidinopiperidine. The crude product was filtered from the reaction mixture and washed with diethyl ether to give the title product (50%, off-white solid).. HPLC-MS: mlz = 450.1 (M+1); Rt: 3.12 min.
Example 219 (General procedure 12)
4-(2-Oxo-2,3-dihydro-benzimidazol-1 -yl)-piperidine-1 -carboxylic acid 4-(5-trif luoromethyl-
pyridin-2-y!oxy)-phenyl ester
The title product was prepared from 4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenol and 1-piperidin-4-yl-1,3-dihydro-benzoimidazof-2-one (44%, oil). HPLC-MS: m/z = 499.1 (M+1); Rt: 4.35 min.
1H NMR (CDCI3): 10.15 (s, 1H), 8.44 (s, 1H), 7.90 (dd, 1H), 7.23 (t, 1H), 7.13-7.20 (m, 4H), 7.06-7.13 (m. 2H), 7.02 (d, 1H), 4.40-4.70 (m, 3H), 2.95-3.30 (m, 2H), 2.40-2.63 (m, 2H), 1.86 (d,2H).
Example 220 (General procedure 12)
3-Diethylcarbamoyl-piperidine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl
ester
The title product was prepared from 4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenol and N,N-diethylnipecotamide (56%, oil). HPLC-MS: /77/z = 466.1 (M+1); R*: 4.51 min.

Example 221 (Genera! procedure 12)
4-CarbamoyI-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-TrlfluoromethyI-pyridin«2-yloxy)-phenol and piperidine-4-carboxylic acid amide. The crude product was subjected to preparative HPLC (47%, white solid). HPLC-MS: m/z= 410.2 (M+1); Rt: 3.45 min.
Example 222 (Genera! procedure 12)
3-CarbamoyI-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The title product was prepared from 4-(5-TrifIuoromethyl-pyridin-2-yloxy)-phenoI and nipeco-tamide. The crude product was purified by preparative HPLC (60%, white solid). HPLC-MS: m/z= 410.2 (M+1); Rt: 3.45 min.
Example 223 (General procedure 14)
Methyl-phenyl-carbamic acid 4-{[4-(methyl-phenyl-carbamoyloxy)-2-oxo-1,2-dihydro-
quinoline-3-carbonyI]-amino}-phenyi ester
The title product was prepared from 4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid (4-hydroxyphenyI)-amide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (6.6%, oil). HPLC-MS: m/z= 563.2 (M+1); Rt: 4.46 min. 1H NMR (CDC!3): 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7.45 (m, 4H), 7.22-7.34 (m, 1H), 7.14-7.21 (t, 1H)f 6.99-7.15 (bs, 1H), 3.44 (s, 3H).
Example 224 (General procedure 14)
Methyl-phenyl-carbamic acid 4-[(4-hydroxy-2-oxo-1,2-dihydro-quinoline-3-carbonyl)-amino]-
phenyl ester
The title product was prepared from 4-hydroxy-2-oxo-1,2-dihydro-quinoIine-3-carboxylic acid (4-hydroxy-phenyI)-amide and N-methyl-N-phenylcarbamoyl chloride (5%,). HPLC-MS: mlz-430.1 (M+1); Rt: 4.80 min, purity: 70%.
Example 225 (General procedure 14) Methyl-phenyl-carbamic acid 4-(4-hydroxy-benzyI)-phenyl ester

The title compound was prepared from 4,4'-dihydroxydiphenylmethane and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative. HPLC (21 %, white crystals which turn red after standing). HPLC-MS: m/z = 324.2 (M+1); Rt: 4.21 min.
Example 226. (General procedure 13)
Methyl-phenyl-carbamic acid 4-(4-trifluoromethyl-benzylcarbamoyI)-phenyl ester
The title product was prepared from 4-(methyI-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 4-trifluoromethyl-benzylamine (94%, white crystals). HPLC-MS: mfz = 429.2 (M+1); R{: 4.35 min.
Example 227 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(butyl-methyI-carbamoyI)-phenyI ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yI ester and /7-butyI-methyl-amine. The crude product was subjected to preparative HPLC (20%, oil). HPLC-MS: mlz= 341.2 (M+1); Rt: 3.96 min.
Example 228 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(methyl-phenethyl-carbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and methyl-phenethyl-amine. The crude product was subjected to preparative HPLC (29.%, oil). HPLC-MS: m/z=389.2 (M+1); Rt: 4.15 min.
Example 229 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(pyridin-2-ylmethyl)-carbamoyl]-phenyI ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 2-aminomethyIpyridine. The crude product was used without further purification (57%, oil). HPLC-MS: m!z= 362.2 (M+1); R,: 2.43 min. 1H NMR (MeOH-cU): 8.50 (d, 1H), 7.92 (d, 2H), 7.83 (dt, 1H), 7.38-7.50 (m, 5H), 7.26-7.37 (m, 2H), 7.15-7.26 (m, 2H), 4.69 (s, 2H), 3.41 (s, 3H).
Example 230 (General procedure 13)

Methyl-phenyl-carbamic acid 4-(2"pyridin-2-yl-ethylcarbamoyI)-phenyI ester
The title product was prepared from 4-(methyl-phenyI-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and 2-aminoethylpyridine. The crude product was used without further purification (26%, oil). HPLC-MS: m/z = 376.2 (M+1); Rt: 2.25 min.
1H NMR (MeOH-d4): 8.51 (d, 1H), 7.87 (dt, 1H), 7.78 (d, 2H), 7.33-7.50 m, 6H)t 7.25-7.33 (m, 1H), 7.18 (d, 2H), 3.74 (t, 2H), 3.41 (bs, 3H), 3.13 (t. 2H).
Example 231 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(2-phenylamino-ethylcarbamoy!)-phenyI ester
The title product was prepared from 4-(methy!-phenyi-carbamoy!oxy)-benzoic acid 2,5-dioxo-pyrrolidine 1-yI ester and N-phenylethylenediamine. The crude product was used without further purification (80%, off-white foam). HPLC-MS: m/z = 390.2 (M+1); Rt: 3.51 min. 1H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7.48 (m, 4H), 7.22-7.34 (m, 1H), 7.15-7.22 (d, 2H), 7.10. (t, 2H), 6.69 (d, 2H), 6.62 (t, 1H), 3.72 (t, 2H), 3.57 (t, 2H), 3.40 (s, 3H), 3.20 (s, 1H).
Example 232 (General procedure 13)
Methyl-phenyl-carbamic acid 4-{3-methyl-butyIcarbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and /so-amylamine. The crude product was used without further purification (95%, oil). HPLC-MS: m/z = 341.2 (M+1); Rt: 3.99 min.
1H NMR (MeOH-d4): 7,82 (d, 2H), 7.36-7.50 (m, 4H), 7.26-7.35 (m, 1H)( 7.15-7.24 (d. 2H), 3.34-3.46 (mr 5H), 1.67 (sept, 1H), 1.50 (q, 2H), 0.96 (d, 6H).
Example 233 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(3,3~dimethyI-butylcarbamoyI)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic add 2,5-dioxo-pyrrolidin-1-yl ester and 3,3-dimethylbutylamine. The crude product was used without further purification(88%, oil). HPLC-MS: m/z= 355.1 (M+1); Rt: 3.10 min. 1H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7.50 (m, 4H), 7.25-7.35 (m, 1H), 7.15-7.25 (d, 2H), 3.33-3.47 (m, 5H), 1.49-1.57 (m, 2H), 0.97 (s, 9H).

Example 234 (General procedure 13)
Methyl-phenyl-carbamic acid 4-[(tetrahydro-furan-2-ylmethyl)-carbamoy!]-phenyl ester
The title product was prepared from 4-(methyI-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and C-(tetrahydro-furan-2-yI)methyIamine. The crude product wasused without further purification (86%, oil). HPLC-MS: m/z = (M+1);Rt: min. 1H NMR (MeOH-d*): 7.84 (d, 2H), 7.35-7.50 (mf 4H), 7.25-7.35 (m, 1H), 7.12-7.25 (d, 2H), 4.10 (qui, 1H)f 3.87 (q, 1H), 3.68-3.82 (m, 1H), 3.41 (s, 3H), 3.35-3.54 (m, 2H), 1.82-2.10 (m, 3H), 1.58-1.72 (m,1H).
Example 235 (General procedure 13)
Methyl-phenyl-carbamic acid 4-cyclohexylcarbamoyI-phenyl ester
The title product was prepared from 4-(methyl-phenyi-carbarnoyloxy)-benzoic acid 2,5-dioxo-pyrroIidin-1-yl ester and cyclohexylamine. The crude product was used without further purification (79%, off-white crystals). HPLC-MS: m/z= 353.2 (M+1); Rt: 3.98 min. 1H NMR (MeOH-d4): 8.18 (df 1H), 7.85 (d, 2H), 7.36-7.52 (m, 4H), 7.25-7.33 (m, 1H), 7.20 (d, 2H), 3.74 (m, 1H), 1.77-1.88 (m, 2H), 1.65-1.77 (m, 2H), 1.60 (d, 1H), 1.24-1.40 (m, 4H), 1-07-1.23 (m, 1H).
Example 236 (General procedure 13)
Methyl-phenyl-carbamic acid 4-cyclopropylcarbamoyl-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and cyclopropylamine. The crude product was used without further purification (97%, oil). HPLC-MS: m/z= 311.2 (M+1); Rt: 3.21 min.
1H NMR (MeOH-d4): 7.81 (d, 2H), 7.36-7.50 (m, 4H), 7.25-7.36 (m, 1H), 7:18 (d, 2H), 3.40 (bs, 3H), 2.78-2.87 (m, 1H), 0.75-0.85 (m, 2H)f 0.57-0.65 (m, 2H).
Example 237 (General procedure 13)
Methyl-phenyl-carbamic acid 4-(cyc!ohexylmethyI-carbamoyl)-phenyl ester
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and C-cyclohexyl-methylamine. The crude product was used without further purification (84%, oil). HPLC-MS: m/z= 367.3 (M+1); Rt:4.28 min.

1H NMR (MeOH-d4):7.81 (d, 2H)f 7.36-7.49 (m, 4H), 7.25-7.32 (m, 1H), 7.19 (d, 2H), 3.40 (bs, 3H), 3.20 (d, 2H), 1.55-1.82 (m, 5H), 1.13-1.35 (m, 4H), 0.90-1.10 (m, 2H).
Example 238
Methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester
A solution of 2-hydroxy-5-nitropyridine (1.40 g, 10.0 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (3.43 g, 10.0 mmol) and triethylamine (0.42 ml, 10.0 mmol) in acetonitrile (25 ml) was heated at 50 °C for 5 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:-heptane (25:75)) followed by crystallisation from ethyl acetate:heptane yielding the title compound (1.13 g, 41% yield) as a white solid.
1H NMR (300MHz, CDCl3): 53.44 (br.s, 3H), 7.17 (br.d, 1H), 7.27-7.45 (mf 5H), 8.49 (br.d, 1H), 9.19 (br.s, 1H); HPLC-MS (Method A): mlz = 296 (M+Na); Rt = 3.45 min.
Example 239
Methyl-phenyl-carbamic acid pyrimidin-2-yl ester
A solution of 2-hydroxypyrimidine hydrochloride (0.40 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.83 ml, 6.00 mmol) in acetonitrile (15 ml) was stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02l ethyl acetate) followed by crystallisation from ethyl acetaterheptane yielding the title compound (0.08 gf 12% yield) as a white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 7.14-7.31 (m, 2H), 7.39 (m, 4H), 8.68 (d, 2H); HPLC-MS (Method A): mlz = 252 (M+Na); Rt = 2.32 min.
Example 240
Methyl-phenyl-carbamic acid 7-chloro-quinolin-4-yl ester
A solution of 7-chloro-4-hydroxyquinoline (0.54 g, 3.00 mmol), 1-methyI-3-(methyl-phenyI-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for. 18 hours. The solvent was evaporated in vacuo and the. residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (40:60)) yielding the title compound (0.87 g, 93% yield) as a colourless

oil which solidified upon standing.
1H NMR (300MHz, CDCI3): £3.47 (br.s, 3H), 7.28-7.58 (m, 8H), 8.05 (br.s, 1H), 8.85 HPLC-MS (Method A): mlz = 313 (M+H); Rt = 3.79 min.
Example 241
Methyl-phenyl-carbamic acid quinoIin-4-yI ester
A mixture of 4-hydroxyquinoIine (0.44 g, 3.00 mmol)), 1-methy!-3-(methyl-phenyI-carbamoyI)-3H-imida2ol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3,00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.75 g, 90% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.49 (br.s, 3H), 7.37 (br.t, 1H), 7.41-7.62 (m, 7H), 7.69 (br.t, 1H), 8.08 (br.d, 1H), 8.87 (d, 1H); HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.56 min.
Example 242
Methyl-phenyl-carbamic acid 5-methyl~isoxazoI-3-yl ester
A mixture of 3-hydroxy-5-methylisoxazole (0.30 g, 3.00 mmol)), 1-methyl-3-(methyI-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02) ethyl acetaterheptane (25:75)) yielding the title compound (0.67 g, 96% yield) as a colourless oil.
1H NMR (300 MHz, CDCI3): £2.40 (s, 3H), 3.40 (br.s, 3H), 6.14 (br.s, 1H), 7.28-7.44 (m, 5H); HPLC-MS (Method A): mlz = 255 (M+Na); Rt = 3.31 min.
Example 243
Methyl-phenyl-rarbamic acid quinoxalin-2-yl ester
A mixture of 2-hydroxyquinoxaline (0.44 g, 3.00 mmol)), 1-methyl-3-(methyI-phenyl-carbamoyI)-3H-imidazoM-ium iodide (1.03 g, 3.00. mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 40 °C for 24 hours. The solvent was evaporated in vacuo and the residue was purified

by flash column chromatography (Si02, ethyl acetate:heptane (30:70)) yielding the title compound (0.65 g, 77% yield) as a white solid..
1H NMR (300 MHz, CDCl3): £3.48 (br.s, 3H), 7.29 (m, 1H), 7.41 (mf 4H), 7.72 (m, 2H), 8.00 (m, 1H), 8.10 (m, 1H), 8.67 (br.s, 1H); HPLC-MS (Method A): mlz = 280 (M+H); Rt = 3.66 min.
Example 244
Methyl-phenyl-carbamic acid 4-methyI-quinolin-2-yI ester
A mixture of 2-hydroxy-4-methylquinoIine (0.48 g, 3.00 mmol) )f 1-methyI-3-(methyl-phenyI-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 50 °C for 4 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70)) yielding the title compound (0.24 g, 27% yield) as a white solid.
1H NMR (300 MHz, CDCI3): £2.70 (s, 3H), 3.49 (br.s, 3H), 7.08 (m, 1H), 7.27 (mf 1H), 7.40 (m, 4H), 7.53 (tf 1H), 7.69 (t, 1H), 7.96 (d, 1H), 8.00 (d, 1H); HPLC-MS (Method A): mfz = 293 (M+H); Rt = 3.88 min.
Example 245
Methyl-phenyl-carbamic acid 3-methyl-quindxaIin-2-yl ester
A mbcture of 2-hydroxy-3-methylquinoxaline (0.48 g, 3.00 mmol)), 1-methyl-3-(methyl-pheny!-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heating at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02r ethyl acetate:heptane (50:50)) yielding the title compound (0.59 g, 67% yield) as a white solid.
1H NMR (300 MHz, CDCI3): £2.61 (br.s, 3H), 3.48 (br.s, 3H), 7.30 (m, 1H), 7.42 (m, 4H), 7.69 (m, 2H), 7.99 (m, 2H); HPLC-MS (Method A): mlz = 294 (M+H); Rt = 3.92 min.
Example 246
Methyl-phenyl-carbamic acid 4,6-dimethyl-pyrimidin-2-yl ester
A solution of 4,6-dimethyl-2-hydroxypyrimidine (0.37 g, 3.00 mmol)), 1-methyl-3-(methyl-

phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmo!) and triethylamine (0,42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.46 g, 60% yield) as a white solid.
1H NMR (300 MHz, CDCl3): 52.48 (s, 6H), 3.43 (br.s, 3H), 6.92 (br.s, 1H), 7.22 (m, 1H), 7.37 (m, 4H); HPLC-MS (Method A): miz = 258 (M+H); Rt = 2.77 min.
Example 247
Methyl-phenyl-carbarnic acid isoquinolin-6-yl ester
A solution of 6-hydroxyquinoIine (0.44 g, 3.00 mmol), 1-methyl-3-(methyl-phenyI-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmo!) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02l ethyl ace-tate:heptane (50:50)) yielding the title compound (0.80 g, 96% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.47 (s, 3H), 7.28 (mf 1H), 7.33-7.54 (m, 6H), 7.59 (s, 1H), 8.08 (d, 2H), 8.86 (m, 1H); HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.63 min.
Example 248
Methyl-phenyl-carbarnic acid quinolin-2-yl ester
A solution of 2-hydroxyquinoline (0.44 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. More acetonitriie (60 ml) was. added and the solution was heated at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (40:60)) yielding the title compound (0.33 g, 40% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.50 (br.s, 3H), 7.14-7.30 (m, 2H), 7.42 (m, 4H), 7.52 (t, 1H), 7.71 (t, 1H), 7.82 (d, 1H), 8.00 (dt 1H), 8.19 (d, 1H); HPLC-MS (Method A): m/z= 279 (M+H); Rt=3.91 min.
Example 249
Methyl-phenyl-carbarnic acid isoquinolin-3-yl ester

A solution of 3-hydroxyisoquinoline (0.44 g, 3.00 mmol), 1-methyi-3-(methyl-phenyI-carbamoy!)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (0.82 g, 99% yield) as a white solid.
1H NMR (300MHz, CDCl3): £3.49 (br,s, 3H)F 7.24 (mf 1H), 7.33-7.47 (m, 5H), 7.51 (t, 1H), 7.63 (t, 1H), 7.77 (d, 1H),7.94 (d, 1H), 9.06 (s, 1H); HPLC-MS (Method A): m/z= 279 (M+H); Rt = 3.68 min.
Example 250
Methyl-phenyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yI ester
A solution of 4-(trifIuoromethyI)-2-pyrimidol (0,49 g, 3.00 mmol), 1-methyI-3-(methyl-phenyI-carbamoyI)-3H-imidazol-1-iurn iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitriie (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate-.heptane (30:70)) yielding the title compound (0.35 g, 39% yield) as a colourless oil.
1H NMR (300MHz, CDCI3): £3.45 (br.s, 3H), 7.28 (m, 1H), 7.38 (m, 4H), 7.52 (br.s, 1H), 8.93 (br.s, 1H); HPLC-MS (Method A): m/z= 320 (M+Na); Rt= 3.58 min.
Example 251
Morpholine-4-carboxyIic acid 4-trifIuoromethyl-pyrimidin-2-yl ester
A solution of 4-(trifluorc>methyI)-2-pyrimidoi (0.49 g, 3.00 mmol), 4-morpholinecarbonyl chloride (0.45 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.51 g, 3.00 mmol) in N,N-dimethylformamide (15 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70 -» 50:50)) yielding the title compound (0.66 g, 80% yield) as a white solid.
1H NMR (300MHz, CDCl3): £3.57-3.81 (m, 8H), 7.57 (d, 1H), 8.97 (d, 1H).; HPLC-MS (Method A): mfz^ 300. (M+Na); Rt = 2.36 min.

Example 252
Methyl-phenyl-carbamic acid 3-nitn>pyridin-2-yI ester
A solution of 2-hydroxy-3-nitropyridine (0.42 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-caitamoyf)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 m!) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate;heptane (40:60)) yielding the title compound (0.41 g, 50% yield) as a yellow solid.
1H NMR (300MHz, CDCI3): £3.41 + 3.58 (2 x br.s, 3H), 7.30 (m, 1H), 7.42 (m, 5H), 8.45 (br.d, 1H), 8.49 (br.s, 1H); HPLC-MS (Method A): mlz = 296 (M+Na); Rt = 3.22 min.
Example 253
Methyl-phenyl-carbamic acid 5-chloro-pyridin-2-yI ester
A solution of 5-chloro-2-pyridol (0.39 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl ace-tate:heptane (30:70)) yielding the title compound (0.78 g, 99% yield) as a white solid. 1H NMR (300MHz, CDCl3): 53.44 (br.s, 3H), 7.00 (br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.69 (d, 1H), 8.30 (d, 1H); HPLC-MS (Method A): mlz = 285 (M+Na); Rt = 3.47 min.
Example 254
Methyl-phenyl-carbamic acid 5-(2-nitro-phenyl)-pyrimidin-2-yl ester
A solution of 5-(2-nitrophenyl)-pyrimidin-2-ol (0.35 g, 1.61 mmol), 1-methyl-3-(methyl-phenyl-carbamoyI)-3tf-imidazol-1-ium iodide (0.55 g, 1.61 mmol). and triethylamine (0.22 ml, 1.61 mmol) in acetonitrile (15 ml) was heated at 50 °C for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl ace-tateiheptane (50:50)) yielding the title compound (0.18 g, 32% yield) as a yellow oil. 1H NMR (300MHz, CDCI3): £3.47 (br.s, 3H), 7.29 (m, 1H), 7.40 (m, 5H), 7.63 (dt, 1H), 7.72 (dt, 1H), 8.10 (d, 1H), 8.61 (br.s, 2H); HPLC-MS (Method A): mlz = 351 (M+H), 373 (M+Na), 723 (2M+Na).; Rt = 3.65 min.

Example 255
Methyl-phenyi-carbamic acid 5-trifluoromethyI-pyridin-2-yl ester
A solution of 2-hydroxy-5-(trifluoromethyI)pyridine (0.49 g, 3.00 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02) ethyl acetate:heptane (15:85)) yielding the title compound (0.59 g, 66% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 7.23 (br.s, 1H), 7.28 (m, 1H)r 7.37 (m, 4H), 7.94 (br.d, 1H), 8.62 (br.s, 1H); HPLC-MS (Method A): m/z= 319 (M+Na); Rt = 3.85 min.
Example 256
Methyl-phenyi-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yI ester
A solution of 3-chloro-5-(trifluoromethyI)"2-pyridinol (0.59 g, 3.00 mmol), 1-methyI-3-(methyl-phenyl-carbamoyI)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (15:85)) yielding the title compound (146 mg, 15% yield) as a white solid.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 7.30 (m, 1H), 7.40 (d, 4H), 8.00 (br.s, 1H), 8.52 (br.s, 1H).; HPLC-MS (Method A): mfz = 353 (M+Na); Rt = 4.29. min.
Example 257
Methyl-phenyi-carbamic acid 5-nitro-3-trifluoromethyl-pyridin-2-yl ester
A solution of 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (0,36 g, 1.73 mmol), N-methyl-N-phenylcarbamoyl chloride (0.44 g, 2.59 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.29 g, 2.59 mmol) in tetrahydrofuran (15 ml), was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the. residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (15:85)) yielding the title compound (0.55 g, 92% yield) as an orange solid..
1H NMR (300MHz, CDCI3): (53.46 (br.s, 3H), 7.23-7.46 (m, 5H), 8.70 (br.s, 1H), 9.37 (br.s, 1H); HPLC-MS (Method A): mlz = 364 (M+H); Rt = 4.08 min.

Example 258
(3-Chloro-phenyI)-methyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester
At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyI-2-hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was removed and stirring was continued at room temperature for 1 hour. (3-ChIorophenyI)-methylamine (0,35 g, 2.50 mmot) was added to one-fourth of the solution. After stirring overnight at room temperature the solvent was evaporated In vacuo and the residue was purified by flash column chromatography (Si02( ethyl acetate:heptane (20:80)) followed by preparative HPLC, yielding the title compound (332 mg, 40%) as a colourless oil. 1H NMR (300MHz, CDCI3): S3.45 (br.s, 3H), 7.23-7.44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H); HPLC-MS (Method A): m/z= 354 (M+H); Rt = 4.03 min.
Example 259
Methyl-m-tolyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester
At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyI-2-hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was removed and stirring was continued at room temperature for 1 hour. Methykn-tolyl-amine (0,30 g, 2.50 mmol) was added to one-fourth of the solution. After stirring overnight at room temperature the solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (20:80)) followed by preparative HPLC, yielding the title compound (51 mg, 7%) as a colourless oil.
1H NMR (300MHz, CDCi3): 52.37 (s, 3H). 3.42 (br.s, 3H), 7.07-7.31 (m, 4H)f 7.52 (br.s, 1H), 8.92 (br.s, 1H); HPLC-MS (Method A): mlz = 334 (M+Na); Rt = 3.92 min.
Example 260
Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester
A solution of 4-trifluoromethyl-2-hydroxypyrimidine (0.49 g, 3.00 mmol), 4-morpholinecarbonyl chloride (0.45 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water and brine were added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The

residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (30:70 -* 50:50)) yielding the title compound (0.66 g, 80% yield) as. a white solid. 'H NMR (300MHz, CDCI3): 53.45 (br.s, 3H), 7.23-7.44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H); HPLC-MS (Method A): mlz = 354 (M+H); Rt =. 4.03 min.
Example 261
Methyl-phenyl-carbamic acid 4,5-dichloro-pyridazin-3-yl ester
A solution of 4,5-dichloro-3-hydroxypyridazine (0.49 g, 3.00 mmol), Af-methyl-W-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in tet-rahydrofuran (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02j ethyl acetate:heptane (20:80)) yielding the title compound (0.12 g, 14% yield) as a white solid. 1H NMR (300MHz, CDCI3): 53.50 (s, 3H), 7.18-7.32 (m. 5H), 7.63 (s, 1H); HPLC-MS (Method A): mlz = 320 (M+Na); Rt = 2.91 min.
Example 262
Methyl-phenyl-carbamic acid 5-benzoylamino-pyridin-2-yI ester
A solution of N-(6-hydroxy-pyridin-3-yl)-benzamide (0.64 g, 3.00 mmol), A/-methyl-/V-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in di-chloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in ethyl acetate and filtered over a short pad of silica. Evaporation of the solvent in vacuo yielded the title compound (0.70 g, 68% yield) as a thick oil.
1H NMR (300MHz, CDCI3): £3.40 (br.s, 3H), 6.90 (br.s, 1H), 7.26 (m, 1H), 7.31-7.44 (m, 6H), 7.50 (m, 1H), 7.88 (d, 2H), 8.08 (dd, 1H)( 8.37 (d, 1H)f 8.79 (br.s, 1H); HPLC-MS (Method A): mlz = 348 (M+H); Rt = 3.49 min.
Example 263
Methyl-phenyl-carbamic acid 5-(cyclohexanecarbonyI-amino)-pyridin-2-yl ester
A solution of cyclohexanecarboxylic acid (6-hydroxy-pyridin-3-yI)-amide (0.66 g, 3.00 mmol),

N-methyl-A/-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1,4-diazabicycio[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.75 g, 71% yield) as a slightly coloured solid.
1H NMR (300MHz, CDCI3): 51.18-1.33 (m, 3H), 1.42-1.59 (m, 2H), 1.60 (m, 1H), 1.77-1.94 (m, 4H), 2.20 (m, 1H), 3.45 (br.s, 3H), 6.91 (br.s, 1H), 7.28 (m, 1H), 7.39 (m, 4H), 7.94 (br.s, 1H)( 8.00 (dd, 1H), 8.20 (d, 1H); HPLC-MS (Method A): mlz = 354 (M+H); Rt = 3.74 rnin.
Example 264
Methyl-phenyl-carbamic acid 4,4-dimethyI-2,6-dioxo-3,4,5)6-tetrahydro-2H-[1 ^bipyridinyl-e1-yl ester
A solution of e'-hydroxy-4,4-dimethyl-4,5-dihydro-SH-tl^lbipyridinyl-^e-dione (0.70 g, 3.00 mmol), /V-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmo!) and 1,4-diazabi-cyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction and subsequently dried in a vacuum oven yielding the title compound (0,75 g, 71% yield) as a white solid.
1H NMR (300MHz, CDCI3): 1.20 (s, 6H), 2.68 (s, 4H), 3.44. (br.s, 3H), 7.14 (br.s, 1H), 7.25 (m, 1H), 7.37 (m, 4H), 7.48 (br.d, 1H), 8.08 (d, 1H); HPLC-MS (Method A): m/z= 368 (M+H); Rt = 3.41 min.
Example 265
Methyl-phenyl-carbamic acid 5-(2f2-dimethyKpropionyIamino)-pyridin-2-yl ester
A solution of A/^e-hydroxy-pyridin-S-yl^^-dimethyl-propionamide (0.58 g, 3.00 mmol), /V-methyl-A/-phenylcarbamoyI chloride (0.51 g, 3.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 1 hour. Water was added and a thick oil was being formed. The water was decanted and the residue was dissolved in dichloromethane. The solution was dried over sodium sulphate, filtered and evaporated in vacuo yielding the title compound (0.55 g, 56% yield) as a brown oil that solidified upon standing. 1H NMR (300MHz, CDCI3): S1.29 (s, 9H), 3.43 (br.s, 3H)f 6.97 (br.s, 1H), 7.26 (m, 1H), 7.38

(m, 4H), 7.64 (br.s, 1H), 8.10 (dd, 1H)f 8.28 (br.s, 1H); HPLC-MS (Method A): m/z= 348 (M+H); Rt = 3.49 min.
Example 266
Methyl-phenyl-carbamic acid 5-(2-cydohexyl-acetylamino)-pyridin-2-yl ester
A solution, of 2-cyclohexyl-N-(6-hydroxy-pyridin-3-yI)-acetamide (0.70 g, 3.00 mmol), N-methyl-W-phenylcarbamoyl chloride (0.51 g, 3.00 mmo!) and 1,4-diazabicyclo[2.2.2]octane (0.34 g, 3.00 mmo!) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.79 g, 72% yield) as a brown solid.
1H NMR (300MHz, CDCI3): $0.86-1.01 (m, 2H), 1.05-1.37 (m, 3H), 1.60-1.78 (m, 5H), 1.83 (m, 1H). 2.13 (d, 2H), 3.46 (br.s, 3H), 6.90 (br.s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.98 (d, 1H), 8.12 (s + br.s, 2H, CH + NH); HPLC-MS (Method A): m/z= 368 (M+H); Rt = 4.04 min.
Example 267
Methyl-phenyl-carbamic acid 5-(4-methoxy-phenoxy)-pyrimidin-2-yI ester
A solution of 5-(4-methoxy-phenoxy)-pyrimidin-2-ol (0.44 g( 2.00 mmol), A/-methyl-/V-phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 -hour. Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetaterheptane yielding the title compound (0.55 g, 79% yield) as an off-white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 3.82 (s, 3H), 6.91 + 7.00 (AB-system, 2 x 2H), 7.26 (m, 1H), 6.39 (m, 4H), 8.33 (s, 2H); HPLC-MS (Method A): m/z = 352 (M+H); Rt = 4.02 min.
Example 268
Methyl-phenyl-carbamic acid 5-(3,4-dichloro-phenoxy)-pyrimidin-2-yl ester
A solution of 5-(3,4-dichloro-phenoxy)-pyrimidin-2-oI (0.51 g, 2.00 mmol), A/-methyl-/V-

phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1,4-diazabicycld[2.2.2]octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates, were collected by. suction. The solids were dissolved in di-chioromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate:heptane yielding the title compound (0.51 g, 65% yield) as an off-white solid.,
1H NMR (300MHz, CDCI3): £3.44 (br.s, 3H), 6.89 (dd, 1H), 7.14 (d, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.44 (d, 1H), 8.42 (s, 2H); HPLC-MS (Method A): mlz = 390 (M+H); Rt = 4.66 min.
Example 269
Methyl-phenyl-carbamic acid 6-pyridin-2-ylmethyl-pyridazin-3-yl ester
A solution of 6-(2-pyridinylmethy!)-3-pyridazinol (100 mg, 0.53 mmol), N-methyl-N-phenylcarbamoyl chloride (91 mg, 0.53 mmol) and 1,4-diazabicyclo[2.2.2]octane (60 mg, 0.53 mmol) in dimethylformamide (10 m!) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02) ethyl acetate) yielding the title compound (70 mgt 41% yield) as a yellow oil.
1H NMR (300MHz, CDCI3): 53.42 (br.s, 3H), 4.50 (s, 2H), 7.11-7.33 (m. 4H), 7.39 (d, 4H), 7.60 (m, 2H), 8.52 (d, 1H); HPLC-MS (Method A): mlz = 321 (M+H); Rt = 1.98 min.
Example 270
Methyl-phenyl-carbamic acid 6-(4-methoxy-benzyI)-pyridazin-3-yl ester
A solution of 6-(2-pyridinylmethyl)-3-pyridazinol (97 mg, 0.45 mmol), /V-methyl-N-phenylcarbamoyl chloride (76 mg, 0.45 mmol) and 1,4-diazabicydo[2.2.2]octane (50 mg, 0.45 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate:heptane (50:50)) yielding the title compound (117 mg, 41 % yield) as a white solid.
1H NMR (300MHz, CDCI3): 53.43 (br.s, 3H), 3.79 (s, 3H), 4.28 (s, 2H), 6.83 (d, 2H), 7.17 (d, 2H), 7.27 (m, 3H), 7.40 (d, 4H); HPLC-MS (Method A): mlz = 350 (M+H); Rt = 3.60 min.

Example 271
Methyl-phenyl-carbamic acid 6-(2,4-dichIoro-benzyl)-pyriclazin-3-yl ester
A solution of 6-(2,4-dichlorobenzyI)-3-pyridazinol (98 mg, 0.38 mmol), A/-methyI-N-phenylcarbamoyl chloride (65 mg, 0.38 mmol) and 1,44iazabicydo[2.2.2]otiane (43 mg, 0.38 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water
was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetaterheptane (40:60)) yielding the title compound (119 mg, 80% yield) as a yellow oil.
1H NMR (300MHz, CDCI3): £3.43 (br.s, 3H), 4.42 (s, 2H), 7.17-7.44 (m, 10H); HPLC-MS (Method A): miz = 388 (M+H); R, = 4.44 min.
Example 272 (General procedure 15)
4-Pyridin-2-yl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)phenyl chloroformate and 1-pyridin-2-yI-piperazine. White crystals, yield 87 %; m.p. 247 - 248 °C; HPLC-MS: m/z = 445 (M+H); IR (KBr): v 1713 (C=0) cm"1.
Example 273 (General procedure 15)
4-(1,3-Benzodioxol-5-yI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2~yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(1,3-benzodioxol-5-yI)-piperazine. The crude product was partitioned between dichlorormethane and 1 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound. Yield 39 %; m.p. 146 -147 °C; 1H NMR (DMSO-cf6): £8.60 - 8.56 (br, 1H), 8.29 -8.20 (dd-like, 1H), 7.31 - 7.20 (m, 5H), 6.84 - 6.72 (d-like, 1H), 6.76 - 6.72 (d-iike, 1H), 6.45 -6.36 (dd-Iike, 1H), 3.81 - 3.47 (br m, 4H), 3.16.-3.00 (br,m, 4H); HPLC-MS: m/z = 488 (M+H); IR (KBr): v 1719 (C=0) cm"1.
Example 274 (General procedure 15)

4-[2-(2-Hydroxyethoxy)ethyI]-piperazine-1 -carboxylic acid 4-(5-trifluorometnyi-pynain-^-yloxy)-phenyl ester
The hydrochloride, of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 2-(2-hydroxyethoxy)ethyl-piperazine. Yield 13 %; 1H NMR (DMSO-cfc): £ 10.8 (br), 8.61 - 8.54 (br, 1H)f 8.30 - 8.21 (dd-Iike, 1H), 7.32 - 7.19 (m, 5H), 4.3 - 3.9 (br, 2H), 3.9 - 3.0 (br m, alicyclics and aiiphatics + water); HPLC-MS: m/z = 456(M+H); !R(KBr):v1724(C=0)cm'1.
Example 275 (General procedure 15)
4-(DiphenyImethyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl chloroformate and 1-(diphenylmethy!)piperazine, white crystals, yield 74 %; m.p. 168- 169 °C;
1H NMR (DMSO-d6); S 12.4 (br, 1H), 8.60 - 8.54 (d-Iike m, 1H), 8.28 - 8.20 (dd-like rn, 1H), 7.98 - 7.82 (br, 2H), 7.55 - 7.15 (br m, 13 H), 5.6 (br, 1H), 4.35 - 3.48 (br, 3H), 3.35 - 3.0 (br, 5H); IR (KBr): v 1723 (C=0) cm"1.
Example 276 (General procedure 15)
4-(4~tert-ButylbenzyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifIuoromethyI~pyridin-2-yloxy)-phenyl chloroformate and 1-(4-ferf-butyIbenzyl)diphenylmethyl)piperazineJ white crystals, yield 56 %; m.p. 274 - 275 °C; HPLOMS: m/z = 514 (M+H); IR (KBr): v 1721 (C=0) cm-Example 277 (General procedure 15)
4-(4-Fluorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-fluorobenzyl)piperazinel white crystals, yield 69 %;

m.p. 240 - 243 °C; HPLC-MS: mfe = 476 (M+H), 498 (M+Na); IR (KBr): v 1720 (C=0) cm"1.
Example 278 (General procedure 15)
4-(2-ThienylethyI)pipera2ine-1-cart>oxylic acid 4-(54rifluoromethyl-pyridin-2-yioxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-thienyIethy[)piperazine, white crystals, yield 62 %; m.p. 236 - 237 °C; 1H NMR (DMSO-cf6): 511.51 (br s, 1H), 8.61 - 8.54 (br m, 1H), 7.48 -7.17 (m, 6H), 7.06 - 6.89 (m, 2H), 4.4 - 3.9 (br, 2H), 3.9 - 2.6 (br m, 15.5 H ~ 12H + water); HPLC-MS: m/z = 478 (M+H); IR (KBr): v 1714 (C=0) cm-1.
Example 279 (General procedure 15)
4-(1-PhenyIethyI)piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester
The crude hydrochloride of the title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yIoxy)-phenyl chloroformate and l~(1-phenylethyl)piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m.p. 242 °C; 1H NMR (DMSO-ofe): S11.56 (br s, 1H), 8.61 - 8.52 (br m, 1H), 8.30. - 8.19 (dd-like m, 1H), 7.77 - 7.31 (br. m, 5H), 7.31 - 7.13 (m, 5H), 4.60 - 3.27 (br m, 6H + water), 3.27 - 2.57 (br, 3H), 1.73 (br d, 3H); IR (KBr): v 1712 (C=0) cm"1.
Example 280 (General procedure 15)
4-Octylpiperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester
The crude hydrochloride of the title compound was prepared from4-(5-trifluoromethyl-pyiidin-2-yloxy)-phenyl chloroformate and 1-(1-phenylethyl)piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m.p. 244-245 °C; 1H NMR (DMSO-cfe): 511-16 (br s, 1H), 8.61 - 8.57 (br m, 1H), 8.30 - 8.20 (dd-like mT 1H)f 7.32 - 7.18 (m, 5H), 4.39 - 3.96 (br, 2H), 3,77 - 3.38 (br, 4H), 3.25 - 2.88 (br, 4H), 1.84 -1.58 (br, 2H), 1.42 - 1.12 (br s, 10H), 0.87 (br t, 3H); IR (KBr): v 1731,1713 (C=0) cm"1.
Example 281 (General procedure 15)
4-(3-Dimethylamino-propyl)-piperazine-1 -carboxylic acid 4«(5"trifluoromethyl-pyridin-2-yloxy)-

phenyl ester
The crude hydrochloride of the title compound was prepared from 4-(5-trifluorornethyl-pyridin-2-yloxy)-phenyI chloroformate and 1-(3-dimethylaminopropyl)piperazine. A suspension of the product in ether was stirred with an excess of HCI in ether and the precipitate was washed with ether and dried to give the dihydrochloride of the title compound as white crystals, m.p. 292 - 293 °C; 'H NMR (DMSO-cf6): S11.35 (br s, 1H), 10.46. (br s, 1H), 8.61 - 8.52 (br m, 1H), 8.31 - 8.17 (m, 1H), 7.35 - 7.16 (m, 5H), 4.45 - 4.00 (br, 2H), 3.80 - 3.45 (br, 4H), 3.30 - 3.01 (br, 6H), 2.78 (br s, 6H), 2.31 - 2.07 (br, 2H); lR (KBr): v 1731, 1713 (C=0) cm-1.
Example 282 (General procedure 15)
4-Pyrimidin-2-yI-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yioxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifiuoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(pyrimidin-2-yI)piperazine. The crude product was dried in vacuo at 50 °C for 80 min and extracted with ether. The ether phase was evaporated and the residue was purified by flash chromatography on silica eluted with ethyl acetate - heptane 1:1 to give the title compound as white needles. Yield 14 %; m.p. 120-121 °C; 1H NMR (DMSO-af6): £8.61 - 8.56 (br, 1H), 8.41 (d, J = 4.8 Hz, 2H)f 8.29 - 8.20 (dd-like, 1H), 7.31 - 7.20 (m, 5H), 6,69 (Hike m, J - 4.8 Hz, 1H), 3.94 - 3.78 (br s, 4H), 3.78 - 3.45 (br d, 4H); HPLC-MS: m/z = 446 (M+H); lR (KBr): v 1719 (C=0) cm"1.
Example 283 (General procedure 15)
4-CycIopropylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-cyclopropyIpiperazine, yield 62 %. Recrystallisation from 0.2 M HCI gave white, crystals, m.p. 238 - 239 °C; 1H NMR (DMSO-cfe): 611.51 (br s, 1H), 8.61 - 8.55 (m, 1H), 8.30 - 8.20 ( m, dd, 1H), 7.32 - 7.19 (m, d+s, 5H), 4.44 - 4.00 (br, 2H), 3.80 - 3.40 (br m, 4H), 3.29 - 2.93 (br m, 4H), 1.28 - 1.05 (br m, 1H), 0.75 - 0.58 (m, 2H), 0.50 - 0.35 (m, 2H).IR (KBr): v 1730, 1713 (C=0) cm"1.
Example 284 (General procedure 15)
4-Methyl-1,4-diazepane-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)phenyl ester

The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-methylhomopiperazine; white crystals, m.p. 210 - 211 °C; 1H NMR (DMSO-d6): 511.27 (br s, 1H), 8.61 - 8,54 (m, 1H), 8.30 - 8.20 (dd-Iike m, 1H). 7.34 - 7.18 (m, 5H), 4.13 - 3.08 (br, 11H, 8H + water), 2.80 (br s, 3H), 2.47 -1.98 (br m, 2H); IR (KBr): v 1723, 1711 (C=0) cm"1.
Example 285. (General procedure 15)
4-Phenethyl-piperazine-1-carboxylic acid 4-(5-trifluorornethyI-pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-y!oxy)-phenyI chloroformate and 1-phenethylpiperazine, yield 54 %. Recrystallisation from 99% EtOH gave white crystals, m.p. 245 - 247 °C; 1H NMR (DMSOcf6): 8 11.72 (br, 1H), 8.63 - 8.53 (br, 1H), 8.31 - 8.19 (dd-Iike m, 1H), 7.44 - 7.16 (m, 10H), 4.44 - 4.01 (br, 2H), 3.83.-3.45 (br, 4H), 3.45 - 2.95 (br, ~8H, 6H + water); IR (KBr): v 1713 (C=0) cm-1.
Example 286 (General procedure 15)
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifiuoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-pyridin-2-yImethyl-piperazine. White crystals, yield 64 %; m.p. 189 - 190 °C; 1H NMR (DMSO-d6): 58.72 - 8.63 (m, 1H), 8.60 - 8.55 (br, 1H), 8.29 -8.20 (dd-Iike, 1H), 8.02 - 7.90 (m( 1H). 7.80 - 7.65 (m, 1H)r 7.56 - 7.45 (m. 1H)f 7.31- 7.22 (m, 5H), 4.52 (br. s, 2H), 4.06 - 3.68 (br s, 4H), 3.68 - 2.93 (br, 4H + NH + water); HPLC-MS: m/z = 459 (M+H); IR (KBr): v 1717 (C=0) cm"1.
Example 287 (General procedure 15)
4-Pyridin-3-y)methyl-piperazine-1 -carboxylic acid 4-(5-trif luoromethyl-pyridin-2-yloxy)-phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine. Trituration with water, filtering and drying of the residue gave white crystals. 1H NMR (DMSO-cfe): £8.78 - 8.51 (m, 3H), 8.30 - 8.18 (dd-Iike, 1H), 8.12 - 8.00 (br d, 1H), 7.57 -7.46 (m, 1H), 7.32 - 7.17 (m, 5H), 4.65

- 4.11 (br, 2H), 4.11 - 2.78 (br m, 6H + water); HPLC-MS: m/z = 459 (M+H); IR (KBr): v 1723
(00) cm"1.
Example 288 (General procedure 15)
4-(3-Phenylpropyl)piperazine-1 -carboxylic acid 4-(54rifluoromethyl-pyridin«2-yloxy)-phenyI
ester
The hydrochloride, of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(3-phenylpropyl)piperazine, yield 68 %. m.p. 235 - 238 °C; 1H NMR(DMSO-d6): 5 11.51 (br, 1H), 8.61 -8.55.(br, 1H), 8.29 - 8.20 (dd-like m, 1H)f 7.38 - 7.16 (m, 10H), 4.38 - 3.96 (br, 2H), 3.83 - 3.40 (br, 4H), 3.30 - 2.91 (br, 4H), 2.75 - 2.57 (Hike m, 2H), 2.20 -1.94 (m, 2H); IR (KBr): v 1715 (C=0) cm"1.
Example 289 (General procedure 15)
4-(4-PhenylbutyI)piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-phenyIbutyI)piperazine, yield 71 %. m.p. 232 - 234 °C;
1H NMR (DMSO-cf6): tf 11.32 (br s, 1H), 8.61 - 8.55 (br, 1H), 8.29- 8.20. (dd-like m, 1H), 7.36
- 7.13 (m, 10H), 4.4Q - 3-97 (br, 2H), 3.81 - 3.39 (br m, 4H), 3.26 - 2.91 (br, 4H), 2.71 - 2.55
(t-like m, 2H)f 1.88 -1.51 (br m, 4H); IR (KBr): v 1728,1713 (C=0) cm"1.
Example 290 (General procedure 15)
4-Benzyl-1,4-diazepane-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title, compound was prepared from 4-(5-trifluoromethyl«pyridin-2-yloxy)-phenyl chloroformate and 1-benzyIhomopiperazine, crude yield 70 %. 0.20 g Of the crude product was heated with 3 ml of water, cooled at 0 °C, the precipitate filtered off and dried; m.p. 231 - 233 °C; 1H NMR (DMSO-of6): 811.38 (br s, 1H), 8.62 - 8.55 (br, 1 H)r 8.30 -8.20 (dd-like m, 1H), 7.76 - 7.60 (br, 2H), 7.52- 7.41 (br m, 3H), 7.32 - 7.19 (m. 5H), 4.38 (br s, 2H), 4.18 - 3.01 (br m, 8H + water), 2.6 - Z0 (brf 2H + DMSO); IR (KBr): v 1726,1710 (C=0) cm"1.

Example 291 (General procedure 15)
4-(3,4-DichlorophenyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyI
ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethy!-pyridin-2-yloxy)-phenyl chloroformate and 1-(3,4-dichlorophenyl)piperazine. The crude product was partitioned between dichlorormethane and 2 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound as white crystals. Yield 28 %; m.p. 115 -116 °C; 1H NMR (DMSO-cf6): 8 8.61 -8.55 (br, 1H), 8.30 - 8.20 (dd-like, 1H), 7.48 - 7.40 (d-Iike,1H), 7.31 - 7.16 (m, 6H), 7.04 - 6.94 (dd-like, 1H), 3.83 - 3.47 (br m, 4H), 3.36 - 3.24 (br s, 4H + water); HPLC-MS: m/z = 512 (M+H); IR (KBr): v 1724,1706 cm"1.
Example 292 (General procedure 15)
4-(4-Fluorophenyt)piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(5~trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-fluoropheny()piperazine. White crystals, yield 20 %; m.p. 131-132 °C; 1H NMR (DMSO-cf6): 8 8.61 - 8.53 (br, 1H), 8.30 - 8.19 (dd-like, 1H), 7.33 -7.17 (m, 5H), 7.17 - 6.95 (m, 4H), 3.85 - 3.47 (br d, 4H), 3.25 - 3.07 (br m, 4H); HPLC-MS: m/z = 462 (M+H); IR (KBr): v 1739,1714 cm'1.
Example 293 (General procedure 15)
4-(2-ChlorophenyI)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl
ester
The the hydrochloride of title compound was prepared from 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-chlorophenyl)piperazine. Drying in vacuo at 50 °C for 3Yz h gave the title compound; 1H NMR (DMSO-of6): £8.61 - 8.55 (br, 1H), 8.29 - 8.20 (dd-like, 1H), 7.53-7.41 (m, 1H), 7.39 - 7.17 (m, 7H), 7.14 - 7.03 (m, 1H), 4.58 (br s, NH + water), 3.85 - 3.55 (br m, 4H), 3.12 - 2.99 (br m, 4H); HPLOMS: m/z = 478 (M+H); IR (KBr): v 1733(C=0)cm-
Example 294 (General procedure 15)
(2-Dimethylamino-ethyl)methyicarbamic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and N,N,N'-trimethyIethylenediamine; m.p. 139 -140 °C; 1H NMR (MeOH-de): 8 8.45 - 8.38 (br, 1H), 8.15 - 8.05 (dd-!ike m, 1H), 7.31 - 7.11 (m, 5H), 3.84 - 3.73 (br m, 2H), 3.54 - 3.38 (br m, 3H), 3.19 (br s, 2H)f 2.99 (br s, 6H); traces of impurities at 3.9 (br) and 3.1 (br); lR (KBr): v 2695, 1705 cm 1 (C=0) cm"1.
Example 295 (General procedure 15) 4-Methylpiperazine-1~carboxyIic acid 4-chIorophenyl ester
The hydrochloride of the title compound was prepared from 4-chlorophenyI chloroformate and 1-methy!piperazinef yield 81 %. White crystals, m.p. 237 - 240 DC; 1H NMR (DMSO-of6): 11.67 (br s, 1H), 7.50, 7.45, 7.24, 7.20 (AB-system, d = 7.47 and 7.22; J = 8.84 Hz, 4H), 4.40 - 3.91 (br, 2H, 3.77 - 2.92 (br m, 6H + water), 2.77 (s, 3H); IR (KBr): v 1717 (C=0) cm"1.
Example 296 (General procedure 15) 4-(4-PhenylbutyI)piperazine-1-carboxylic acid 4-chlorophenyl ester
The hydrochloride of the title compound was prepared from 4-chlorophenyl chloroformate and 1-(4-phenylbutyl)piperazine, yield 86 %. White crystals, m.p. 230 - 232 °C; 1H NMR (DMSO-cfe): 8 11.43 (br, 1H), 7.51 - 7.43 (d-like m, 2H), 7.33 - 7.15 (m, 7H), 4.33 - 3.95 (br, max at 4.21 and 4,10 ppm; 2H), 3.72 - 3.36 (br m, 4H), 3.22 - 2.96 (br, max at 3.10 ppm, 4H)f 2.62 (t, J= 7.54 Hz, 2H), 1.84 - 1.69 (m, 2H), 1.69 -1.54 (m, 2H) ppm; IR (KBr): v 1736,1720 (C=0) cm'1.
Example 297 (General procedure 15)
4-[2-(2-Hydroxyethoxy)ethyI]piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl
ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 2-(2-hydroxyethoxy)ethyI-piperazine. Pale powder, m.p. 176 -178 °C; 1H NMR (MeOH-d4): 5 Two AB-systems: 7.68 - 7.58 (d-like, 2H)

and 7.29 - 7.04 (m, 6H); 4.74 - 3.18 (complex, 16 H, partly overlapping with MeOH-tf4); HPLC-MS m/z = 455 (M+H), 477 (M+Na), Rt= 3.08 min.; IR (KBr): v 1718 (C=0) cm"1.
Example 298 (General procedure 15)
4-(1-EthylpropyI)piperazine-1-carboxyIic acid 4-(4-trifluoromethylphenoxy)phenyl ester
The hydrochloride of the title compound was. prepared from 4-(4-trifluoromethylphenoxy)phenyl chloroformate and 1-(1-ethylpropyI)piperazine, yield 74 %. White crystals, 1H NMR (DMSO-d6): 510.59 (brs, 1H), 2 AB-systems: 7.81 -7.70 (d-like, 2H) and 7.31 - 7.09 (m, 6H); 4.38 -3.99 (br s, 2H), 3.90 - 3.38 (br, 4H), 3.33- 2.99 (br, 3H), 2.01 - 1.77 (m, 2H), 1.77 -1.49 (m, 2H), 0.98 (t, 6H); HPLC-MS m/z = 437 (M+H).
Example 299 (General procedure 15)
4-CycIoheptyipiperazine-1-carboxylic acid 4-(4-trifIuoromethy!-phenoxy)pheny! ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate. and 1-cydoheptylpiperazine. The crude product was partitioned between dichlorormethane and aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate - heptane (1:4) and the precipitate was collected by filtration and dried to give the title compound. White crystals, 1H NMR (MeOH-cf4): 8 Two AB-systems: 7.68 - 7.58 (d-like, 2H) and 7.23 - 7.04 (m, 6H); 3.86 - 3.50 (br d, 4H), 2.98 - 2.66 (br, 5H), 2.04 - 1.37 (m, 12H); HPLC-MS m/z = 463 (M+H); IR (KBr): v 1730,1707 crrf1.
Example 300 (General procedure 15)
4-Cyclohexylpiperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 1-cyclohexylpiperazine, yield 80 %. White crystals, m.p. 290 - 291 °C, 1H NMR (DMSO-cf6): S10.82 (br s, 1H), 2 AB-systems: 7.83 -7.69 (d-like, 2H) and 7.32 - 7.10 (m, 6H); 4.40 -4.02 (br, 2H), 3.75 - 3.39 (br, 4H), 3.31- 2.98 (br, 3H), 2.23 - 2.02 (m, 2H), 1.92 - 1.74 (m, 2H), 1.70 - 0.97 (mf 6H); HPLC-MS m/z = 449 (M+H); IR (KBr): v 1717 (C=0) cm"1.
Example 301. (General procedure 15)

4-(4-ChIorobenzyI)piperazine-1-carboxylic acid 4-(4-trifluoromethyIphenoxy)phenyi ester
The hydrochloride of the title compound was prepared from 4-(4-
trffluoromethylphenoxy)phenyl chloroformate and 1-(4-chlorobenzyI)piperazine, yield 86 %. White crystals, rap. 232 - 234 °C; 1H NMR (DMSO-cf6): 8 11.92 (br s( 1 H)r 3 AB-systems: 7.83 - 7.62 (Hike, 4H) and 7.62 - 7.48 (d-like, 2H). and 7.32 - 7.07 (m, 6H); 4.51 - 3.95 (br s at 4.37 ppm overlapping with br signal at 4.2 ppm, 4H), 3.95 - 2.95. (br m, 9H: 6H + water); IR (KBr): v 1717 (C=0)crrf1.
Example 302 (General procedure 15)
4-(4~Methylbenzy!)piperazine-1-carboxylic acid 4-(4-trifluorornethylphenoxy)phenyl ester
The hydrochloride of the title compound was prepared from 4-(4-
trifluoromethylphenoxy)phenyl chloroformate and 1-(4-methyIbenzyI)piperazine, yield 96 %. White crystals, m.p. 250-252°C; HPLC-MS m/z = 472 (M+H); IR (KBr): v 1720 (C=0) cm-1.
Example 303 (General procedure 15)
4-(4-Methoxybenzyl)piperazine-1 -carboxylic acid 4-(54rifluoromethyl-pyridin-2-yloxy)-phenyI
ester
The hydrochloride of the title, compound was prepared from 4-(5-trifIuoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(4-methoxybenzyI)piperazine, yield 78 %. White crystals, m.p. 237 - 238 °C; HPLOMS m/z = 488 (M+H); IR (KBr): v. 1719 (C=0) cm'1.
Example 304 (General procedure 15)
4-(2-Chloro-6-fluoro-benzyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-
phenyl ester
The hydrochloride of the title compound was prepared from 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate and 1-(2-chloro-6-fluorobenzyl)piperazine. White crystals, m.p. 204 - 205 °C (from ethanol); HPLC-MS m/z = 510 (M+H); (R (KBr): v 1726 (C=0) cm"1;
Example 305 (General procedure 15)
4-(3-Methoxyphenyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester

The hydrochloride of the title compound was prepared from 4-(4-trffluoromethylphenoxy)phenyl chloroformate and 1-(3-methoxyphenyI)piperazine. White crystals, m.p. 168-171 °C (sinters at 160 °C); HPLC-MS m/z = 473(M+1); IR (KBr): v 1739, 1716(C=0)cm~1.
Example 306 (General procedure 15)
4-Benzyl-piperazine-1-carboxylic acid 4-(3-chloro-5-trifIuoromethyl-pyridin-2-yIoxy)phenyI ester
The hydrochloride of the title compound was prepared from 4-(3-chIoro-5-trifluoromethyI-pyridin-2-yloxy)-phenyl chloroformate and 1-benzyl-piperazine, yield 94 %. White crystals; m.p. 111-113 °C (resolidifies) and 114-115 °C; HPLC-MS m/z = 492 (M+H).
Example 307 (General procedure 8)Methy!-phenyl-carbamic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy~4-iodopyrazoIe and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, oil). 1H NMR (300MHz; CDCI3): 8 3.44 (bs, 3H), 7.30-7.48 (m, 7H).; HPLC-MS : m/z = 343.9 (M+1);R« = 4.12min.
Example 308 (General procedure 8)Methyi-phenyl-carbamic acid benzotriazol-1-yl ester
The title compound was prepared from 1-hydroxybenzotriazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, crystallizes slowly). 1H NMR (300MHz; CDCI3): S 3.50 (bs, 3H), 7.37-7.57 (m, 8H), 8.04 (d, 1H).; HPLC-MS: mlz = 269.0 (M+1); Rt = 3.69 min.
Example 309 (General procedure 8)Methyl-phenyl-carbamic acid [1,2,3]triazolo[4,5-b]pyridin-3-yl ester
The title compound was prepared from [l^spYiazolofrS-^pyridin-S-ol and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified

by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, oil).
1H NMR (300MHz; CDCI3): 5 3.50 (bs, 3H), 7.30-7.60 (m, 6H), 8.40. (d, 1H), 8.75 (d, 1H);
HPLC-MS: m/z = 270.0 (M+1); Rt = 3.18 min.
Example 310 (General procedure 8)MethyI-pheny!-carbamic acid 3-(2-nitro-phenyI)-pyrazol-1-yI ester
The title compound was prepared from 1-hydroxy-3-(2-nitrophenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (94%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 6.44 (bs, 1H), 7.30-7.50 (m, 7H), 7.58 (dt, 1H), 7.72-7.78 (m, 2H); HPLC-MS : mlz= 339.1 (M+1); Rt = 4.15 mln.
Example 311 (General procedure 8)Methyl-phenyl-carbarnic acid 3-(4-nitro-phenyI)-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-3-(4-nitrophenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, yellow crystals). 1H NMR (300MHz; CDCI3): 5 3.47 (bs, 3H), 6.70 (bd, 1H), 7.32-7.50 (m, 6H), 7.94 (d, 2H), 8.26 (d, 2H); HPLC-MS : m/z= 339.1 (M+1); Rt = 4.41 min.
Example 312 (General procedure 8)Methyl-phenyl-carbamic acid 3-pyridin-2-yl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-pyridyI)pyrazoIe and N-methyl-N-phenylcarbamoyl chloride, applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, oil). 1H NMR (300MHz; CDCI3): S 3.48 (bs, 3H), 6.95 (d, 1H), 7.20 (dd, 1H), 7.30-7.48 (m, 6H), 7.70 (dt, 1H), 7.93 (d, 1H), 8.61 (d, 1H); HPLC-MS : m/z= 295.1 (M+1); Rt = 2.75 min.
Example 313 (General procedure 8)Methyl-phenyl-carbamic acid 3-thiophen-2-yl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-thienyI)pyrazole and N-methyl-N-

phenyicarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (66%, oil). 1H NMR (300MHz; CDCI3): S 3.46 (bs, 3H), 6.48 (bd, 1H), 7.03 (dd, 1H), 7.25 (dd, 1H), 7.30-7.48 (m, 7H); HPLC-MS : mlz = 300.1 (M+1); Rt = 4.16 min..
Example 314 (General procedure 8)MethyI-phenyI-carbamic acid 3-(2-fluoro-phenyI)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3-(2-fIuorophenyi)pyrazoIe and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil). 1H NMR (300MHz; CDCI3): 8 3.48 (bs, 3H), 6.75 (bt, 1H), 7.07-7.47 (mf 9H), 7.97 (dt, 1H); HPLC-MS : mlz = 312.1 (M+1); Rt = 4.45 min.
Example 315 (General procedure 8)Methyl-phenyl-carbamic acid 3-bromo-pyrazoi-1-y! ester
The title compound was prepared from 1-hydroxy-3-bromopyrazo!e and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil).
1H NMR (300MHz; CDCI3): 8 3.43 (bs, 3H), 6.31 (d, 1H), 7.26-7.48 (m, 6H).; HPLC-MS : mlz = 298.0 (M+1); Rt= 3.97 min.
Example 316 (General procedure 8)Methyl-phenyI-carbamic acid 5-iodo-pyrazol-1-y! ester
The title compound was prepared from 1-hydroxy-5-iodopyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (64%, oil).
1H NMR (300MHz; CDCI3): 8 3.48 (bs, 3H), 6.42 (df 1H), 7.28-7.47 (m, 6H).; HPLC-MS : mlz = 343.9 (M+1); Rt= 3.81 min.
Example 317 (General procedure 8)Methyl-phenyl-carbamic acid 2-chloro-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-chloroimidazoIe, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (77%, oil).
1H NMR (300MHz; CDC!3): 8 3.45 (bs, 3H), 6.90 (bs, 1H)f 7.07 (bs, 1H), 7.35-7.40 (m, 3H),
7.46 (bt, 2H); HPLC-MS : mlz = 251.9 (M+1); Rt = 3.29 min.
Example 318 (General procedure 8)Methyl-phenyl-carbamic acid 4-(4-methoxy-phenyI)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-4-(4-methoxyphenyI)pyrazo!e and N-methy!-N-phenylcarbamoyt chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (6%, oil). 1H NMR (300MHz; CDCI3): 5 3.45 (bs. 3H), 3.82 (s, 3H)( 6.90 (d, 2H), 7.30-7.48 (m, 7H), 7.54 (bs, 2H); HPLC-MS : mlz= 346.1 (M+23); R( = 4,16 min.
Example 319 (General procedure 8)Methy!-phenyl-carbarnic acid 5-benzoyI-pyrazoI-1-yI ester
The title compound was prepared from 1-hydroxy~5-benzoy]pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (30%, crystals). 1H NMR (300MHz; CDCI3): S 3.48 (bs, 3H), 6.69 (bs, 1H), 7.27-7.52 (m, 8H), 7.63 (t, 1H), 7.79 (d, 2H); HPLC-MS: mlz = 344.0 (M+23); Rt = 4.41 min.
Example 320 (General procedure 8)Methyl-phenyl-carbamic acid 5-(4-methoxy-phenyl)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-5-(4-methoxyphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (38%, yellow crystals).
1H NMR (300MHz; CDCI3): 8 3.33 (bs, 3H), 3.86 (s, 3H), 6.34. (d, 1H), 6.95 (d, 2H), 7.25-7.45 (m, 8H); HPLC-MS: mlz = 324.1 (M+1); Rt = 4.27 min.
Example 321 (General procedure 8)Methyl-phenyI-carbamic acid 5-(4-dimethyiamino-phenyl)-pyrazol-1-yl ester

The title compound was prepared from 1-hydroxy-5-(4-dimethylaminophenyl)-pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (27%, crystals). 1H NMR (300MHz; CDCI3): 8 3.02 (s, 6H). 3.35 (bs, 3H), 6.30 (d, 1H), 6.72 (d, 2H), 7.30-7.46 (m, 8H); HPLC-MS : m/z= 337.1 (M+1); Rt = 4.11 min.
Example 322 (General procedure 8)Methyl-phenyl-carbamic acid 4,5-diiodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4,5-diiodopyrazole and N-methy!-N-phenylcarbamoyl chloride applying the genera! procedure 8. The. crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (76%, crystals). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 7.30-7.50 (m, 6H).; HPLC-MS : mlz = 369.9 (M+1); Rt = 4.56 min.
Example 323 (General procedure 8)MethyI-phenyl-carbamic acid 5-thiophen-2-yl-pyrazol-1-yi ester
The title compound was prepared from 1-hydroxy-5-(2-thienyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8, The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (51%, crystals). 1H NMR (300MHz; CDCI3): 8 3.44 (bs, 3H), 6.45 (bs, 1H), 7.09 (dd, 1H), 7.26 (bs, 1H); 7.28-7.49 (m, 7H); HPLC-MS : m/z= 300.1 (M+1); Rt = 4.18 min.
Example 324 (General procedure 8)MethyI-phenyl-carbamic acid 2-(4-methoxy-phenyI)-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-(4-methoxyphenyI)imidazole, hydrochloride and N-methyl-N-phenylcarbamoyI chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, crystals).
1H NMR (300MHz; CDCI3): 8 3.33 (bs, 3H), 3.86 (s, 3H), 6.92 (d, 2H), 7.04 (d, 1H), 7.10 (bs, 1H), 7.28 (d, 2H), 7.34-7.50 (m, 3H), 7.60 (bd, 2H); HPLC-MS: m/z= 324.1 (M+1); Rt = 2.87 min.

Example 325 (General procedure 8)MethyI-phenyl-carbamic acid 2-methylsulfanyI-imidazoI-1-yl ester
The title compound was prepared from 1-hydroxy-2-methylsulfanyI-imidazole hydrochloride and N-methyl-N-phenylcarbamoyi chloride applying the general procedure 8, The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil). 1H NMR (300MHz; CDC!3): S 2.56 (s, 3H), 3.44 (bs, 3H), 7.00 (bs, 1H), 7.08 (bs, 1H), 7.32-7.49 (m, 5H); HPLC-MS : miz = 264.1 (M+1); Rt = 2.99 mln.
Example 326 (General procedure 8)MethyI-phenyI-carbamic acid 3,5-bis-(4-methoxy-phenyl)-pyrazo!-1-yI ester
The title compound was prepared from 1-hydroxy-3,5-bis-(4-methoxyphenyI)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (29%, beige crystals). 1H NMR(300MHz; CDC!3): 5 3.35 (bs, 3H), 3.84 (s, 3H)F 3.88 (s, 3H), 6.57 (s, 1H), 6.92 (d, 2H), 6.97 (d, 2H), 7.25-7.48 (m, 7H)t 7.74 (d, 2H); HPLC-MS : miz = 881.2 (2M+23); Rt = 5.26 min.
Example 327 (General procedure 8)MethyI-phenyI-carbamic acid 4-(4-fIuoro-phenyl)-5-(4-methoxy-phenyl)-3-(4-methylphenyl)-pyrazol-1 -yl ester
The title compound was prepared from 1-hydroxy-4-(4-fluoropheny!)-5-(4-methoxyphenyI)-3-(4-methylphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the. general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (11%, crystals).
1H NMR (300MHz; CDCI3): S 2.32 (s, 3H), 3.32 (bs, 3H), 3.83 (s, 3H), 6.87 (d, 2H), 6.93 (d, 2H), 7.12-7.48 (m, 13H); HPLC-MS : m/z= 530.2 (M+23); Rt = 6.04 min.
Example 328 (General procedure 8)Methyl-phenyl-carbamic acid 4-benzyl-5-(4-methoxy-phenyl)-3-(methylphenyl)-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-benzyI-5-(4-methoxyphenyl)-3-(4-methylphenyOpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-

heptane) (14%, oil).
1H NMR (300MHz; CDCI3): S 2.31. (s, 3H), 3.31 (bs, 3H), 3.83 (s, 3H), 3.95 (s, 2H), 6.89 (d,
2H), 7.08-7.39 (mt 13H), 7.43 (d, 2H); HPLC-MS : mfz = 504.2 (M+1); Rt = 6.11 min.
Example 329 (General procedure 8)Methyl-phenyl-carbamic acid 4-acetyl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-acetyIpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the genera! procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, oil). 1H NMR (300MHz; CDCI3): S 2.44 (s, 3H), 3.44 (bs, 3H), 7.32-7.48 (m, 5H), 7.78 (bs, 1H)( 7.85 (bs, 1H).
Example 330. (General procedure 8)Methyl-phenyl-carbamic acid 2-(4-nitro-phenyI)-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-(4-nitrophenyI)imidazole, hydrochloride
and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude
product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, yellow
crystals).
1H NMR (300MHz; CDCI3): 5 3.38 (bs, 3H), 7.16 (s, 1H), 7.20 (s, 1H), 7.31 (d, 2H), 7.38-7.61
(m, 3H), 7.86 (bs, 2H), 8.25 (d, 2H).
Example 331 (General procedure 8)Methyl-phenyl-carbamic acid 2-chloro-5-(4-methylphenyl)-imidazol-1 -yl ester
The title compound was prepared from 1-hydroxy-2-chloro-5-(4-methylphenyl)imidazole, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (80%, oil).
1H NMR (300MHz; CDCI3): 8 2.40 (s, 3H), 3.33 (bs, 3H), 7.00 (s, 1H), 7.19-7.29 (m, 6H), 7.35-7.50 (m, 3H).
Example 332 (General procedure 8)MethyI-phenyl-carbamic acid 4-formyl-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-formylpyrazole and N-methyl-N-

phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (73%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 7.29-7.50 (m, 5H), 7.84 (bs, 1H), 7.90 (bs, 1H), 9.83 (s, 1H).
Example 333 (General procedure 8)Methyl-phenyl-carbamic acid 4-hydroxymethyl-pyrazoI-
1-yI ester
The title compound was prepared from 1-hydroxy-4-hydroxymethylpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, oil). *H NMR (300MHz; CDCI3): 8 2.33 (bs, 1H), 3.40 (bs, 3H), 4.50 (s, 2H), 7.28-7.46 (m, 7H).
Example 334 (General procedure 8)Methyl-phenyl-carbamic acid 4-phenylethynyI-pyrazol-1-yi ester
The title compound was prepared from 1-hydroxy-4-phenyIethynyIpyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (40%, yellow crystals). 1H NMR (300MHz;. CDCI3): 8 3.42 (bs, 3H), 7.30-7.58 (m, 12H).
Example 335 (General procedure 8)Methyl-phenyl-carbamic acid 2-bromo-imidazol-1-yl ester
The title compound was prepared from l-hydroxy-2-bromoimidazole, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil). 1H NMR (300MHz; CDCI3): 8 3.45 (bs, 3H), 6.98 (bd, 1H), 7.11 (bs, 1H), 7.33-7.50 (m, 5H); HPLC-MS : mlz = 296.0 (M+1); Rt = 2.90 min.
Example 336 (General procedure 8)Methyl-phenyl-carbamic acid 2-phenylsulfanyl-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2- phenylsulfanylimidazole hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude

product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (61%, oil). 1H NMR (300MHz; CDC!3): 8 3.35 (s, 3H), 7.12 (bd, 1H), 7.17-7.39 (m, 11H); HPLC-MS : m/z= 326.0 (M+1); Rt = 3.65 min.
Example 337 (General procedure 8)Morpholine-4-carboxylic acid imidazoI-1-yl ester
The title compound was prepared from 1-hydroxyimidazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by preparative HPLC (water-acetonitriIe-0.1%TFA) (36%, crystals).
1H NMR (300MHz; CDCI3): 8 3.57 (bs, 2H), 3.66 (bs, 2H), 3.78 (t, 4H), 7.12 (bs, 1H), 7.15 (bt, 1H), 7.90 (s, 1H); HPLC-MS : m/z= 198.1 (M+1); Rt= 0.36 min.
Example 338 (General procedure 8)MorphoIine-4-carboxyIic acid 2-bromo-imidazol-1-yI ester
The title compound was prepared from 1-hydroxy-2-bromoimidazole, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (98%, crystals). 1H NMR (300MHz; CDCI3): 8 3.60 (bs, 2H), 3.71 (bs, 2H), 3.80 (t, 4H), 7.02 (d, 1H), 7.18 (d, 1H); HPLC-MS : m/z = 276.0 (M+1); Rt = 1.73 min.
Example 339 (General procedure 8)Morpholine-4-carboxylic acid 2-chloro-imidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-chloroimidazoIe, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (54%, oil).
1H NMR (300MHz; CDCI3): 8 3.58 (bs, 2H), 3.68 (bs, 2H), 3.69 (t, 4H), 6.94 (d, 1H), 7.10 (d, 1H); HPLC-MS : mlz = 232.0 (M+1); Rt = 1.69 min.
Example 340 (General procedure 8)Morpholine-4-carboxylic acid 2-phenylsulfanyl-irnidazol-1-yl ester
The title compound was prepared from 1-hydroxy-2-phenylsulfanylimidazole, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc) (98%, oil).
1H NMR (300MHz; CDCI3): S 3.46 (bs, 4H)f 3.66 (bs, 4H), 7.15 (d, 1H). 7.18-7.31 (m, 6H);
HPLC-MS : mlz* 306.1 (M+1); Rt = 2.75 min.
Example 341 (General procedure 8)Morpholine-4-carboxyIic acid 2-(4-methoxy-phenyI)-imidazol-1-yl ester
The title compound was prepared from 14iydroxy-2-(4-methoxypheny!)imidazole, hydrochloride and 4-morphoIine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (49%, crystals). 1H NMR (300MHz; CDCI3): 8 3.51 (bs, 2H), 3.62-3.76 (m, 6H), 3.86 (s, 3H), 6.96 (d, 2H), 7.08 (d, 1H), 7.11 (d, 1H), 7.70 (d, 2H); HPLC-MS : m/z= 304.1 (M+1); Rt= 1.81 min.
Example 342 (General procedure 8)Morpholine-4-carboxylic acid 4-bromo-pyrazol-1-yI ester
The title compound was prepared from 1-hydroxy-4-bromopyrazoIe and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (85%, crystals).
1H NMR (300MHz; CDCI3): 5 3.57 (bs, 2H), 3.68 (bs, 2H), 3.79 (t, 4H), 7.35 (d, 1H), 7.43 (d, 1H); HPLC-MS :m/z= 298.0 (M+23); Rt= 2.46 min.
Example 343 (General procedure 8)Morpholine-4-carboxylic acid 4-iodo-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, crystals).
1H NMR (300MHz; CDCl3): 5 3.56 (bs, 2H), 3.66 (bs, 2H), 3.77 (t, 4H), 7.41 (d, 1H), 7.44 (d, 1H); HPLC-MS : mfz = 324.0 (M+1); Rt = 2.65 min.
Example 344 (General procedure 8)Morpholine-4-carboxylic acid 3,4,5-tribromo-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3,4,5-tribromopyrazole and 4-morpholine carbonyi chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, crystals).

1H NMR (300MHz; CDCI3): S 3.59 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H); HPLC-MS : mlz = 455.6 (M+23); Rt= 3.91 min.
Example 345 (General procedure 8)
Morpholine-4-carboxylic acid 3-(4-methoxy-phenyl)-pyrazoM-yl ester
The title compound was prepared from 1-hydroxy-3-(4-methoxyphenyI)pyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, crystals). 1H NMR (300MHz; CDCI3): 5 3.58 (bs, 2H), 3.71 (bs, 2H), 3.79 (t, 4H), 3.84 (s, 3H), 6.53 (d, 1H), 6.92 (d, 2H), 7.40 (d, 1H), 7.71 (d, 2H); HPLC-MS : /n/z= 326.0 (M+23); Rt = 3.21 min.
Example 346 (General procedure 8)MorphoIine-4-carboxylic acid 3-thiophen-2-yi-pyrazoi-1-yl ester
The title compound was prepared from 1-hydroxy-3-(2-thienyI)pyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (75%, crystals).
1H NMR (300MHz; CDCl3): 8 3.57 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H), 6.51 (d, 1H), 7.04 (dd, 1H), 7.26 (dd, 1H), 7.34 (dd, 1H)f 7.40 (d, 1H); HPLC-MS : mlz = 280.0 (M+1); Rt = 3.12 min.
Example 347 (General procedure 8)MorphoIine-4-carboxyIic acid pyrazol-1-yl ester
The title compound was prepared from 1-hydroxypyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (94%, crystals).
1H NMR (300MHz; CDCI3): S 3.57 (bs, 2H), 3.69 (bs, 2H)t 3.79 (t, 4H), 6.32 (t, 1H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS: mlz = 198.0 (M+1); Rt = 1.18 min.
Example 348 (General procedure 16)4-Methyl-piperazine-1-carboxy!ic acid pyrazoM-yl ester
The title compound was prepared from 1-hydroxypyrazole and N-methylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (water-acetonitrile-0.1% TFA) (17%, salt with TFA).

1H NMR (300MHz; CDCl3): 8 2.36 (s, 3H), 2.50 (bt, 4H), 3.59 (bs, 2H), 3.71 (bs, 2H), 6.31 (t, 1H), 7.38 (dd, 1H), 7.40 (dd, 1H); HPLC-MS : mlz =211.0 (M+1); Rt = 0.40 min.
Example 349 (General procedure 16)4~CyclopentyI-piperazine-1-carboxyIic acid pyrazoM-yl ester
The title compound was prepared from 1-hydroxypyrazoIe and N-cycIopentylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (wa-ter-acetonitrile-0.1 % TFA) (34%, salt with TFA).
1H NMR (300MHz; CDCI3): 8 1.45-2.01 (m, 8H), 2.70 (bs, 4H), 2.92 (bs, 1H), 3.55 (bt, 1H), 3.63 (bs, 2H), 3.77 (bs, 2H), 6.31 (t, 1H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : m/z = 265.1 (M+1); Rt= 0.54 min.
Example 350 (General procedure 16)4-Phenyi-piperazine-1-carboxylic acid pyrazoI-1-y! ester
The title compound was prepared from 1-hydroxypyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals).
1H NMR (300MHz; CDCI3): 8 3.25 (bt, 4H), 3.72 (bs, 2H), 3.85 (bs, 2H), 6.33 (t. 1H), 6.92-6.98 (m, 3H), 7.27-7.33 (m, 2H), 7.38 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : mlz = 273.1 (M+1); ' Rt = 3.06 min.
Example 351 (General procedure 16)4-Pyridin-2«yI-piperazine-1-carboxylic acid pyrazol-1-yl ester
The title compound was prepared from 1-hydroxypyrazole and 1-(2-pyridyI)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (59%, crystals).
1H NMR (300MHz; CDCI3): 8 3.62-3.85 (m, 8H), 6.32 (t, 1H), 6.66-6.72 (m, 2H), 7.39 (dd, 1H), 7.42 (dd, 1H), 7.53 (dt, 1H), 8.21 (d, 1H); HPLC-MS : m/z= 274.1 (M+1); Rt = 0.63 min.
Example 352 (General procedure 16)4-Pyrimidin-2-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester

The title compound was prepared from 1-hydroxypyrazole and 1-(2-pyrimidyI)piperazine ap- . plying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (57%, crystals).
1H NMR (300MHz; CDCI3): 8 3.65 (bs, 2H). 3.78 (bs, 2H), 3.95 (bs, 4H), 6.32 (t, 1H), 6.5S (t, 2H), 7.38 (dd, 1H), 7.42 (dd, 1H), 8.35 (d, 1H); HPLC-MS : mlz= 275.2 (M+1); Rt = 2.14 min.
Example 353 (General procedure 16)4-Benzo[1,3]dioxoI-5-yI-piperazine-1-carboxylic acid pyrazol-1-yI ester
The title compound was prepared from 1-hydroxypyrazole and 1-Benzo[1,3]dioxol-5-ylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (92%, crystals).
1H NMR (300MHz; CDCI3): 8 3.11 (bt, 4H), 3.71 (bs, 2H), 3.83 (bs, 2H), 5.93 (s, 2H), 6.32 (t, 1H), 6.39(dd, 1H),6.57(d, 1H), 6.74(d, 1H), 7.37 (dd, 1H), 7.41 (dd, 1H); HPLC-MS : mlz = 317.2 (M+1); Rt = 2.96 min.
Example 354 (General procedure 16)4-BenzyI-piperazine-1~carboxy!ic acid 4-iodo-pyrazoI-l-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-benzylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (32%f oil).
1H NMR (300MHz; CDCI3): 8 2.53 (bs, 4H), 3.57 (bs, 4H), 3.67 (bs, 2H), 7.28^7.38 (m, 5H)f 7.40 (d, 1H), 7.43 (d, 1H); HPLC-MS : m/z = 413.0 (M+1); Rt = 1.75 min..
Example 355 (General procedure 16)4-Cydopentyl-piperazine-1-carboxylic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazoIe and N-cyclopentylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane-3% Et3N) (61%, crystals). 1H NMR (300MHz; CDCI3): 8 1.33-1.94 (m, 8H), 2.46-2.61 (m, 5H), 3.57 (bt, 2H), 3.67 (bt, 2H), 3.63 (bs, 2H). 3.77 (bs, 2H), 7.40 (d, 1H), 7.44 (d, 1H); HPLC-MS : m/z= 391.1 (M+1); Rt= 1.31 min.

Example 356 (General procedure 16)4-(4-Fluoro-benzyI)-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-(4-fluorobenzy!)piperazine applying the genera! procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals). 1H NMR (300MHz; CDCI3): S 2.50 (t, 4H), 3.51 (s, 2H), 3.57 (bt, 2H), 3.66 (bt, 2H), 7.02 (t, 2H), 7.29 (dd, 2H), 7.40 (d, 1H), 7.43 (d, 1H); HPLC-MS : m/z= 431.0 (M+1); Rt = 1.79 min.
Example 357 (General procedure 16)4-PhenyI-piperazine-1-carboxyIic acid 4-iodo-pyrazol-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (52%, crystals).
1H NMR (300MHz; CDCI3): S 3.25 (t, 4H), 3.72 (bs, 2H), 3.81 (bs, 2H), 6.90-6.97 (m, 3H), 7.30 (t, 2H), 7.41 (d, 1H), 7.47 (d, 1H); HPLC-MS : m/z= 399.1 (M+1); Rt = 3.91 min.
Example 358 (General procedure 16)4-Pyridin-2-y!-piperazine-1-carboxyIic acid 4-iodo-pyrazoI-1-yl ester
The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-(2-pyridyI)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (45%, crystals).
1H NMR (300MHz; CDCI3): S 3.62-3.82 (m, 8H), 6.66-6.72 (m, 2H), 7.42 (d, 1H), 7.47 (d, 1H), 7.54 (dtf 1H), 8.22 (d, 1H); HPLC-MS : m/z = 400.0 (M+1); Rt = 1.47 min.
Example 359 (General procedure 16)4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4-iodo-pyrazoH-yl ester
The. title compound was prepared from 1-hydroxy-4-iodopyrazole and 1~(2-pyrimidyl)piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (10%, crystals). 'H NMR (300MHz; CDCI3): 5 3.62 (bs, 2H), 3.72 (bs, 2H), 3.95 (bs, 4H), 6.58 (t, 2H), 7.41 (d, 1H), 7.46 (d, 1H), 8.36 (d, 1H); HPLC-MS : mlz = 401.0 (M+1); Rt = 3.09 min.

Example 360 (General p