Title of Invention

DERIVATIVES OF N-' (1,5-DIPHENYL-1 H-PYRAZOL-3-YL) SUPHONAMIDE WITH CB1 RECEPTOR AFFINITY

Abstract The invention relates to compounds of formula (I): Wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 are as defined herein. The invention also relates to the preparation method thereof and to the use of same in therapeutics.
Full Text DERIVATIVES OF N'-(I,5-DIPHENYL-1H-PYRAZOL-3-YL)
SULFONAMIDE WITH CB1 RECEPTOR AFFINITY
The subjection of the present invention is N-[ (1,5-
diphenyl-1H-pyrazol-3-yl)methyl]sulfonamide
derivatives, their preparation and their therapeutic
application.
Diphenylpyrazole derivatives having affinity for the CB1
cannabinoid receptors have been described in particular
in patents EP 0 576 357, EP 0 656 354 and US 5 624 941.
Novel N-[(1,5-diphenyl-1H-pyrazol-3-yl)methyl]sulfon-
amide derivatives which possess CB1 cannabinoid receptor
antagonist properties have now been found.
The subject of the present invention is compounds
corresponding to the formula (I):

in which:
R1 represents
• a (C1-C6)alkyl;
• a (C3-C7)cycloalkyl which is unsubstituted or
substituted once or several times with a
(C1-C3) alkyl group;
• a (C3-C7) cycloalkylmethyl which is
unsubstituted or substituted once or several
times on the carbocycle with a (C1-C3) alkyl;
• a phenyl which is unsubstituted or mono-,


di- or trisubstituted with a substituent
independently chosen from a halogen atom, a
(C1-C4) alkyl, a (C1-C3) alkoxy, a cyano, a
trifluoromethyl radical, a trifluoromethoxy
radical, an S(O)nAlk group, a (C1-C3)
alkylcarbonyl group, a phenyl;
• a benzyl which is unsubstituted or mono- or
disubstituted with a substituent
independently chosen from a halogen atom, a
(C1-C3) alkyl, a (C1-C3) alkoxy; a
trifluoromethyl radical;
• a thienyl which is unsubstituted or
substituted with a halogen atom or with an
isoxazolyl;
R2 represents a hydrogen atom or a (C1-C3) alkyl;
R3 represents a hydrogen atom or a (C1-C5) alkyl;
R4, R5, R6, R7, R8 and R9 each independently
represent a hydrogen atom, a halogen atom, a
(C1-C7) alkyl, a (C1-C5) alkoxy, a trif luoromethyl
radical or an S(O)nAlk group;
n represents 0, 1 or 2;
Alk represents a (C1-C4) alkyl.
The compounds of formula (I) may contain one or more
asymmetric carbon atoms. They can therefore exist in
the form of enantiomers or diastereoisomers. These
enantiomers, diastereoisomers and mixtures thereof,
including the racemic mixtures, form part of the
invention.
The compounds of formula (I) may exist in the form of
bases or addition salts with acids. Such addition salts
form part of the invention.
These salts are advantageously prepared with
pharmaceutically acceptable acids but the salts of
other acids useful for the purification or isolation of
the compounds of formula (I) also form part of the
invention.


The compounds of formula (I) may also exist in the form
of hydrates or solvates, namely in the form of
associations or combinations with one or more molecules
of water or with a solvent. Such hydrates and solvates
also form part of the invention.
The expression halogen atom is understood to mean a
bromine, chlorine, fluorine or iodine atom.
The expression (C1-C3) alkyl or respectively (C1-C4) alkyl,
(C1-C5) alkyl, (C1-C6) alkyl or (C1-C7) alkyl is understood
to mean a linear or branched alkyl radical of one to
three carbon atoms or respectively of one to four
carbon atoms, of one to five carbon atoms, of one to
six carbon atoms or of one to seven carbon atoms, such
as the methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl,
hexyl, isohexyl or heptyl radical.
The expression (C1-C3) alkoxy or respectively (C1-C5)
alkoxy is understood to mean a linear or branched
alkoxy radical of one to three carbon atoms or
respectively of one to five carbon atoms, such as the
methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-
butoxy, tert-butoxy, pentoxy or isopentoxy radical.
The expression (C3-C7)cycloalkyl is understood to mean a
cyclic alkyl group of 3 to 7 carbon atoms, such as the
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or
cycloheptyl group.
Among the compounds of formula (I), which are the
subject of the invention, there may be mentioned the
preferred compounds which are defined as follows:
R1 represents
• an ethyl, an isopropyl, an n-butyl;
• a cyclohexyl;
• a cyclohexylmethyl;


• a 2-chlorophenyl, a 3-chlorophenyl, a 2-
fluorophenyl, a 3-chloro-4-fluorophenyl, a
4-bromo-2-ethylphenyl, a 3-methylphenyl, a
4-tert-butylphenyl, a 3,5-dimethylphenyl, a
3-methoxyphenyl, a 4-methoxyphenyl, a 3-
cyanophenyl, a 4-cyanophenyl, a 2-
(trifluoromethyl)phenyl, a 3-
(trifluoromethyl)phenyl, a 4-(trifluoro-
methyl) phenyl, a 3,5-bis(trifluoromethyl)-
phenyl, a 2-(trifluoromethoxy)phenyl, a 3-
(trifluoromethoxy)phenyl, a 2-
(methylsulfonyl)phenyl, a 3-(methylsulfonyl)
phenyl, a 3-acetylphenyl, a 3-biphenyl, a 2-
biphenyl;
• a 3-chlorobenzyl, a 2-fluorobenzyl, a 4-
fluorobenzyl, a 3-(trifluoromethyl)benzyl, a
4-(trifluoromethyl)benzyl;
• a 5-bromo-2-thienyl; a 5-isoxazol-3-yl-2-
thienyl;
and/or R2 represents a hydrogen atom or a methyl;
and/or R3 represents a methyl or an ethyl;
and/or R4 represents a hydrogen atom;
and/or R5 is at the 4-position of the phenyl and
represents a bromine, chlorine or fluorine atom,
or a methoxy;
and/or R6 represents a hydrogen atom;
and/or R7 represents a hydrogen atom;
and/or R8 is at the 4-position of the phenyl and
represents a hydrogen atom, a chlorine atom, a
fluorine atom;
and/or R9 is at the 2-position of the phenyl and
represents a chlorine or fluorine atom;
in the form of a base or of an addition salt with an
acid, and in the form of a hydrate or a solvate.
Among the latter preferred compounds, those
particularly preferred are the compounds of formula (I)
for which:
R1 represents


• an ethyl, an isopropyl, an n-butyl;
• a cyclohexyl;
• a cyclohexylmethyl;
• a 2-chlorophenyl, a 3-chlorophenyl, a 2-
fluorophenyl, a 3-chloro-4-fluorophenyl, a
4-bromo-2-ethylphenyl, a 3-methylphenyl, a
4-tert-butylphenyl, a 3,5-dimethylphenyl, a
3-methoxyphenyl, a 4-methoxyphenyl, a 3-
cyanophenyl, a 4-cyanophenyl, a 2-
(trifluoromethyl)phenyl, a 3-
(trifluoromethyl)phenyl, a 4-(trifluoro-
methyl) phenyl, a 3,5-bis(trifluoromethyl) -
phenyl, a 2-(trifluoromethoxy)phenyl, a 3-
(trifluoromethoxy)phenyl, a 2-
(methylsulfonyl)phenyl, a 3-(methylsulfonyl)
phenyl, a 3-acetylphenyl, a 3-biphenyl, a 2-
biphenyl;
• a 3-chlorobenzyl, a 2-fluorobenzyl, a 4-
fluorobenzyl, a 3-(trifluoromethyl)benzyl, a
4-(trifluoromethyl)benzyl;
• a 5-bromo-2-thienyl; a 5-isoxazol-3-yl-2-
thienyl;
R2 represents a hydrogen atom or a methyl;
R3 represents a methyl or an ethyl;
R4 represents a hydrogen atom;
R5 is at the 4-position of the phenyl and
represents a bromine, chlorine or fluorine atom,
or a methoxy;
R6 represents a hydrogen atom;
R7 represents a hydrogen atom;
R8 is at the 4-position of the phenyl and
represents a hydrogen atom, a chlorine atom, a
fluorine atom;
R9 is at the 2-position of the phenyl and
represents a chlorine or fluorine atom;
in the form of a base or of an addition salt with an
acid, and in the form of a hydrate or a solvate.
Among the compounds of formula (I) which are the


subject of the invention, the following compounds may
be mentioned in particular:
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]butane-1-
sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-
cyclohexanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-
cyclohexylmethanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
chlorobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyL -1H-pyrazol-3-yl] methyl] -4-tert-
butylbenzenesulf onamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-4-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl] methyl] -2- (methylsulf onyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-1-(3-chlorophenyl)
me thanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-1-[3-
(trifluoromethyl)phenyl]methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-chloro-4-
fluorobenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-


methyl-1H-pyrazol-3-yl]methyl]-butane-1-
sulfonamide;
3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl) -4-methyl-1H-pyrazol-3-yl] methyl]
benzenesulfonamide;
4-tert-butyl-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-lfl-pyrazol-3-yl]methyl]-4-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl] -2-
(trifluoromethoxy)benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-2-(methylsulfonyl)
benzenesulfonamide;
3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-ltf-pyrazol-3-yl]methyl]-
4-fluorobenzenesulfonamide;
4-bromo-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-
2-ethylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl] ethanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethy1-1H-pyrazol-3-yl]methyl]propane-2-
sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethy1-1H-pyrazol-3-yl]methyl]butane-1-sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-lif-pyrazol-3-yl] methyl] -
cyclohexanesulfonamide;


N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethy1-1H-pyrazol-3-yl]methyl]-1-
cyclohexylmethanesulfonamide;
N- [ [5- (4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-
chlorobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl] methyl] -2-
chlorobenzenesulfonamide;
N- [ [5- (4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-
me thylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-tert-
butylbenzenesulf onamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl) -4-
ethyl-1H-pyrazol-3-yl]methyl]-3-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-(trifluoromethoxy)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-ltf-pyrazol-3-yl]methyl]-2-(trifluoromethoxy)
benzenesulfonamide;
3-acetyl-N-[[5-(4-bromophenyl)-1-(2,4-
dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;


N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]biphenyl-3-
sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-[4-
(trifluoromethyl)pheny1]methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-[3-
(trifluoromethyl)phenyl]methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl] methyl] -3,5-
dimethylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3,5-bis
(trifluoromethyl)benzenesulfonamide;
3-chloro-N-[[1-(2-chlorophenyl)-5- (4-
chlorophenyl) -4-methyl-1H-pyrazol-3-yl] methyl]
benzenesulfonamide;
N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-2-
fluorobenzenesulfonamide;
N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-
methy1-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-
methy1-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-(2-fluorophenyl)
methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl] -1- (4-fluorophenyl)
me thanesulfonamide;


5-bromo-N-[[5-(4-bromophenyl)-1-(2, 4-
dichlorophenyl)-4-ethyl-ltf-pyrazol-3-yl]methyl]
thiophene-2-sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-5-isoxazol-3-
ylthiophene-2-sulfonamide;
3-chloro-N-[[1-(2,4-dichlorophenyl)-5-(4-
methoxyphenyl)-4-methyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
N-[[1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-4-
methy1-1H-pyrazol-3-yl]methyl]-3-
methylbenzenesulfonamide;
in the form of a base or of an addition salt with an
acid, and in the form of a hydrate or of a solvate.
In the text that follows, the expression protecting
group Pg is understood to mean a group which makes it
possible, on the one hand, to protect a reactive
functional group such as a hydroxyl or an amine during
synthesis and, on the other hand, to regenerate the
intact reactive functional group at the end of the
synthesis. Examples of protecting groups and methods of
protection and deprotection are given in "Protective
Group in Organic Synthesis", Green et al., 2nd Edition
(John Wiley & Sons, Inc., New York), 1991.
The expression leaving group is understood to mean, in
the text which follows, a group which can be easily
cleaved from a molecule by rupturing a heterolytic
bond, with departure of an electron pair. This group
can thus be easily replaced by another group during a
substitution reaction, for example. Such leaving groups
are, for example, halogens or an activated hydroxyl
group such as a methanesulfonate, benzenesulfonate, p-
toluenesulfonate, triflate, acetate and the like.
Examples of leaving groups and references for their
preparation are given in "Advances in Organic
Chemistry", J. March, 3rd Edition, Wiley Interscience,
1985, p. 310-316.

In accordance with the invention, the compound of
formula (I) may be prepared according to a method which
is characterized in that: a compound of formula:

in which R2, R3, R4, R5, R6, R7, R8 and R9 are as defined
for a compound of formula (I), is reacted, in the
presence of a base and in a solvent, with a sulfonyl
halide of formula:

in which R1 is as defined for a compound of formula (I)
and Hal represents a halogen atom.
Optionally, the compound of formula (I) is converted to
one of its addition salts with an acid.
The reaction is carried out in the presence of a base
such as triethylamine or diisopropylethylamine, in a
solvent such as dichloromethane or tetrahydrofuran, and
at a temperature between room temperature and the
reflux temperature of the solvent. The reaction is
preferably carried out using a compound of formula
(III) in which Hal represents a chlorine atom.
According to another variant of the method, it is

possible to prepare the compound of formula (I) in
which R2 represents a (C1-C3) alkyl by reacting a
compound of formula (I) in which R2 = H with a (C1-C3)
alkyl halide, in the presence of a base such as sodium
hydride, or potassium carbonate, in a solvent such as
N,N-dimethylformamide and at a temperature between room
temperature and the reflux temperature of the solvent.
The compounds of formula (I) thus obtained may be
subsequently separated from the reaction medium and
purified according to conventional methods, for example
by crystallization or chromatography.
The compounds of formula (II) are prepared by reacting
a compound of formula:

in which R3, R4, R5, R6, R7, R8 and R9 are as defined for
a compound of formula (I) and Y represents a leaving
group as defined above, preferably a halogen atom or an
activated hydroxyl group such as a methanesulfonate,
benzenesulfonate, p-toluenesulfonate or triflate group,
with a compound of formula:

in which R2 is as defined for a compound of formula (I).
The reaction is carried out in a solvent such as N,N-
dimethylformamide, acetonitrile, dichloromethane,
toluene or propan-2-ol, and in the presence or in the
absence of a base. When a base is used, it is chosen
from organic bases such as triethylamine, N,N-

diisopropylethylamine or N-methylmorpholine. The
reaction is carried out at a temperature of between 0°C
and the reflux temperature of the solvent.
According to one variant, it is also possible to
prepare a compound of formula (II) in which R2 = H by
reacting a compound of formula (IV) in which Y = Cl
with 1, 3, 5, 7-tetraazatricyclo [3 . 3 .13.7] decane (or
hexamethylenetetramine) followed by hydrolysis with a
strong acid such as hydrochloric acid.
The compounds of formula (III) are commercially
available or are described in the literature, or may be
prepared according to methods which are described
therein, for example in J. Org. Chem. USSR, 1970, _6,
2454-2458; J. Am. Chem. Soc, 1952, 74., 2008; J. Med.
Chem., 1977, 20(10), 1235-1239; EP 0 469 984;
WO 95/18105.
For example, the compounds of formula (III) may be
prepared by halogenation of the corresponding sulfonic
acids or of their salts, for example of their sodium or
potassium salts. The reaction is carried out in the
presence of a halogenating agent such as phosphorus
oxychloride, thionyl chloride, phosphorus trichloride,
phosphorus tribromide or phosphorus pentachloride, with
no solvent or in a solvent such as a halogenated
hydrocarbon or N,N-dimethylformamide and at a
temperature of between -10°C and 200°C.
The compounds of formula (IV) are prepared from the
compounds of formula:


in which R3, R4, R5, R6, R7, R8 and R9 are as defined for
a compound of formula (I), according to conventional
methods cited above.
Thus, for example, when in a compound of formula (IV) Y
represents a halogen atom, a compound of formula (VI)
is treated with a halogenating agent such as PCl5, PBr3,
HBr or BBr3, in a solvent such as dichloromethane and at
a temperature between 0°C and room temperature.
When, in a compound of formula (IV), Y represents a
methanesulfonate, a benzenesulfonate, a p-toluene-
sulfonate or a trifluoromethanesulfonate, a compound of
formula (VI) is reacted with a sulfonyl chloride of
formula X-SO2-Cl in which X represents a methyl, a
phenyl, a p-tolyl or a trifluoromethyl. The reaction is
carried out in the presence of a base such as
triethylamine, pyridine or N,N-diisopropylethylamine,
in a solvent such as dichloromethane or toluene and at
a temperature between -20°C and the reflux temperature
of the solvent.
The compounds of formula (V) are known.
The compounds of formula (VI) are prepared by a
reaction for reducing the compounds of formula:

in which R3, R4, R5, R6, R7, R8 and R9 are as defined for
a compound of formula (I) and Z represents a hydroxyl

or a (C1-C2) alkoxy.
The reaction is carried out in the presence of a
reducing agent such as sodium borohydride or lithium
aluminum hydride, in a solvent such as tetrahydrofuran,
and at a temperature between -20°C and room
temperature. When a compound of formula (VII) in which
Z = OH is reduced, the acid may be activated beforehand
by reaction with ethyl chloroformate in the presence of
triethylamine.
The compounds of formula (VII) are known and are
prepared according to known methods such as those
described in EP 0656 354, EP 0576 357 or in
WO 00/46209.
The following examples describe the preparation of
certain compounds in accordance with the invention.
These examples are not limiting and merely illustrate
the present invention. The numbers for the compounds
exemplified refer to those given in Table V below,
which illustrates the chemical structures and the
physical properties of a few compounds according to the
invention.
In the preparations and in the examples, the following
abbreviations are used:
ether : diethyl ether
iso-ether : diisopropyl ether
DMSO : dimethyl sulfoxide
DMF : N,N-dimethylformamide
THF : tetrahydrofuran
DCM : dichloromethane
AcOEt : ethyl acetate
DIPEA : diisopropylethylamine
TFA : trifluoroacetic acid
hydrochloric ether 2N : 2N solution of hydrochloric
acid in diethyl ether
m.p. : melting point


RT : room temperature
b.p. : boiling temperature
HPLC : high performance liquid chromatography
silica H : silica 60 H gel marketed by Merck
(DARMSTAD)
buffer solution pH = 2 : solution of 16.66 g of KHS04
and 32.32 g of K2SO4 in 1 liter of water.
The nuclear magnetic resonance spectra are recorded at
200 MHz in DMSO-d6. For the interpretation of the
spectra, the following abbreviations are used:
s: singlet, d: doublet, t: triplet, m: unresolved
complex, mt: multiplet, bs: broad s.
The compounds according to the invention are analyzed
by LC/UV/MS (liquid chromatography/UV detection/mass
spectrometry) coupling. The molecular peak (MH+) and the
retention time (tr) in minutes are measured.
The apparatus used, marketed by Agilent, is composed of
a chromatograph HP 1100 equipped with an Agilent diode
array detector and an MSD Quad quadripole mass
spectrometer.
Method A:
There is used an Xterra Waters® MS C18 column, marketed
by Waters, 2.1 x 30 mm, 3.5 µm, at room temperature,
flow rate 1 ml/minute.
The eluant is made up as follows:
solvent A: 0.025% trifluoroacetic acid (TFA) in
water;
solvent B: 0.025% TFA in acetonitrile.
Gradient: the percentage of solvent B varies from 0 to
100% within 2 minutes with a plateau at 100% B for 1
minute.
The UV detection is carried out between 210 nm and

400 nm and the mass detection in chemical ionization
mode at atmospheric pressure.
Method B:
There is used a Symmetry C18 column 2.1 x 50 mm,
3.5 µm, at 30°C, flow rate 0.4 ml/minute.
The eluant is made up as follows:
solvent A: 0.005% trifluoroacetic acid (TFA) in
water at pH 3.15;
solvent B: 0.005% TFA in acetonitrile.

The UV detection is carried out at X = 210 nM and the
mass detection is carried out in positive electrospray
mode (ESI).
Method C:
There is used a Symmetry C18 column 2.1 x 50 mm,
3.5 urn, at 30°C, flow rate 0.4 ml/minute.
The eluant is made up as follows:
solvent A: 0.005% TFA in water at pH 3.15;
solvent B: 0.005% TFA in acetonitrile.


The UV detection is carried out at X = 210 nM and the
mass detection is carried out in positive electrospray
mode (ESI) .
Method D:
There is used an Xterra MS C18 column 2.1 x 50 mm,
3.5 ) µm, at 30°C, flow rate 0.4 ml/minute.
The eluant is made up as follows:
solvent A: 10 nM ammonium acetate (AcONH4) in water
at pH 7;
solvent B: acetonitrile.

The UV detection is carried out at X = 220 nM and the
mass detection is carried out in positive electrospray
mode (ESI).
Method E:
There is used an Xterra MS C18 column 2.1 x 50 mm,
3.5 (µm, at 30°C, flow rate 0.4 ml/minute.
The eluant is made up as follows:
solvent A: 10 nM AcONH4 in water at pH 7;
solvent B: acetonitrile.



PREPARATIONS:
1. Preparations of the compounds of formula (VII)
Preparation 1.1
5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-
1H-pyrazole-3-carboxylic acid
(VII) : R3 = -CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-C1; Z = -OH.
A) Lithium salt of ethyl 4-(4-bromophenyl)-3-methyl-
2-oxo-4-oxydobut-3-enoate
A solution of 43 g of the lithium salt of
hexamethyldisilazane in 300 ml of ether is cooled to
-60°C, a solution of 50 g of 4-bromopropiophenone is
added dropwise in 500 ml of ether and the mixture is
kept stirring until the temperature rises to -30°C.
38 g of diethyl oxalate are then added and the mixture
is kept stirring for 18 hours, the temperature being
allowed to rise to RT. The precipitate formed is
drained, it is washed with ether and it is dried under
vacuum. 62 g of the expected product are obtained.
B) Ethyl 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazole-3-carboxylate
To a solution of 30 g of the compound obtained in the
preceding step in 150 ml of acetic acid are added 20 g
of 2,4-dichlorophenylhydrazine hydrochloride and the
mixture is heated under reflux for 3 hours. After
cooling to RT, the reaction mixture is poured into a
water/ice mixture, extracted with ether, the organic
phase is washed with a saturated NaCl solution, dried
over MgS04, the solvent is partially evaporated under
vacuum and the crystallized product formed is drained.
33.4 g of the expected product are obtained.
C) 5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-
1H-pyrazole-3-carboxylic acid
To a solution of 26 g of the compound obtained in the


preceding step in 50 ml of EtOH are added 6.5 g of KOH
and then 20 ml of water and the mixture is heated under
reflux for 2 hours. After cooling to RT, the reaction
mixture is poured into a water/ice mixture containing
10 ml of concentrated HCl, the precipitate formed is
drained, washed with water and dried under vacuum. 24 g
of the expected product are obtained.
Preparation 1.2
Methyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazole-3-carboxylate
(VII) : R3 = -CH3; R4 = H; R5 = 4-Cl; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-Cl; Z = -OCH3.
A) 5- (4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-lif-pyrazole-3-carboxylic acid
This compound is prepared according to the operating
methods described in EP 0 656 354B.
B) Methyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazole-3-carboxylate
To a solution of 30 g of the compound obtained in the
preceding step in 500 ml of MeOH are added 3 g of para-
toluenesulfonic acid and the mixture is heated under
reflux for 2 hours. The reaction mixture is
concentrated under vacuum by half, the precipitate
formed is drained, washed with MeOH and dried. 30 g of
the expected product are obtained.
Preparation 1.3
5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-
1H-pyrazole-3-carboxylic acid
(VII) : R3 = -CH2CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;
R8 = 4-C1; R9 = 2-C1; Z = -OH.
This compound is prepared according to the procedures
described in WO 00/46209.
By following the procedures described in Preparations 1
above, the compounds of formula (VII) assembled in

TABLE I below are prepared.

2. Preparations of the compounds of formula (VI).
Preparation 2.1
[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methanol
(VI) : R3 = -CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-Cl.
A mixture of 24 g of the compound obtained in
Preparation 1.1 in 200 ml of THF is cooled to -10°C,
7.8 ml of triethylamine are added, followed dropwise by
5.38 ml of ethyl chloroformate and the mixture is kept
stirring for 15 minutes at -10°C. 6.3 g of sodium
borohydride are then added all at once and at a
temperature of less than -10°C, followed dropwise by
100 1 of MeOH and the mixture is kept stirring for 30
minutes at 0°C. The reaction mixture is hydrolyzed by
adding 100 ml of 10% HC1, it is concentrated under
vacuum, the residue is taken up in water, extracted
with AcOEt, the organic phase is washed with a
saturated NaCl solution, dried over MgS04 and the


solvent is evaporated under vacuum. The residue is
chromatographed on silica gel, eluting with the
cyclohexane/AcOEt mixture (75/25; v/v) . 22 g of the
expected product are obtained.
Preparation 2.2
[5- (4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methanol
(VI) : R3 = -CH3; R4 = H; R5 = 4-C1; R6 = H; R7 = H;
R8 = 4-C1; R9 = 2-C1.
A solution of 30 g of the compound obtained in
Preparation 1.2 in 500 ml of THF is cooled to -5°C,
4.6 g of lithium aluminum hydride are added in small
portions and while maintaining the temperature between
-5°C and 0°C and the mixture is kept stirring for 1
hour at RT. The reaction mixture is cooled to 0°C,
hydrolyzed by adding 20 ml of 1N NaOH, the inorganics
are filtered, washed with THF and the filtrate is
concentrated under vacuum. The residue is extracted
with ether, the organic phase is washed with a
saturated NaCl solution, dried over Na2SO4 and the
solvent is partially evaporated under vacuum. The
precipitate formed is drained, washed with ether and
dried. 25 g of the expected product are obtained.
Preparation 2.3
[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-
1H-pyrazol-3-yl] methanol
(VI) : R3 = -CH2CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-Cl.
A mixture of 24.6 g of the compound obtained in
Preparation 1.3 in 200 ml of THF is cooled to -10°C,
7.8 ml of triethylamine are added, followed dropwise by
5.38 ml of ethyl chloroformate and the mixture is kept
stirring for 15 minutes at -10°C. 6.3 g of sodium
borohydride are then added all at once and at a
temperature of less than -10°C, followed dropwise by
100 ml of MeOH. The reaction mixture is hydrolyzed at
0°C by adding 100 ml of 10% HC1 and then concentrated

under vacuum. The residue is extracted with AcOEt, the
organic phase is washed twice with 50 ml of a saturated
NaCl solution, dried over Na2SO4 and the solvent is
evaporated under vacuum. The residue is chromatographed
on silica gel, eluting with the cyclohexane/AcOEt
mixture (60/40; v/v) . 20 g of the expected product are
obtained.
By following the procedures described in Preparations 2
above, the compounds of formula (VI) assembled in
TABLE II below are prepared.


3. Preparations of the compounds of formula (IV)
Preparation 3.1
5-(4-Bromophenyl)-3-(chlorophenyl)-1-(2,4-
dichlorophenyl) -4-methyl-1H-pyrazole


(IV) : R3 = -CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-Cl; Y = Cl.
A solution of 20 g of the compound obtained in
Preparation 2.1 in 250 ml of DCM is cooled to 0°C under
a nitrogen atmosphere, 10.6 g of phosphorus
pentachloride are added in small fractions and at a
temperature of less than 5°C and the mixture is kept
stirring for 2 hours, the temperature being allowed to
rise to RT. The reaction mixture is poured into 150 ml
of a water/ice mixture and the mixture is kept stirring
for 10 minutes. The mixture is extracted with DCM, the
organic phase is washed with a 5% NaHCO3 solution, with
a saturated NaCl solution, dried over MgSO4 and the
solvent is evaporated under vacuum. 24 g of the
expected product are obtained.
Preparation 3.2
3-(Chloromethyl)-5-(4-chlorophenyl)-1-(2, 4-
dichlorophenyl) -4-methyl-lJf-pyrazole
(IV) : R3 = -CH3; R4 = H; R5 = 4-Cl; R6 = H; R7 = H;
R8 = 4-Cl; R9 = 2-Cl; Y = Cl.
A solution of 25 g of the compound obtained in
Preparation 2.2 in 250 ml of DCM is cooled to 0°C under
a nitrogen atmosphere, 14.8 g of phosphorus
pentachloride are added in small fractions and at a
temperature of between 0°C and 5°C and the mixture is
kept stirring for 3 hours, the temperature being
allowed to rise to RT. The reaction mixture is poured
into 200 ml of water and kept stirring for 10 minutes.
After decantation, the organic phase is washed with a
saturated NaHCO3 solution, with a saturated NaCl
solution, dried over Na2SO4 and the solvent is
evaporated under vacuum. 25 g of the expected product
are obtained in the form of a meringue.
Preparation 3.3
5-(4-Bromophenyl)-3-(chloromethyl)-1-(2,4-
dichlorophenyl)-4-ethyl-1H-pyrazole
(IV) : R3 = -CH2CH3; R4 = H; R5 = 4-Br; R6 = H; R7 = H;

R8 = 4-Cl; R9 = 2-Cl; Y = Cl
This compound is prepared according to the procedure
described in Preparation 3.2 from 9 g of the compound
obtained in Preparation 2.3 in 200 ml of DCM and 4.6 g
of phosphorus pentachloride. 9.4 g of the expected
product are obtained.
By carrying out the procedures as described in
Preparations 3 above, the compounds of formula (IV)
assembled in TABLE III below are prepared.

4. Preparations of the compounds of formula (II)
Preparation 4.1
[[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]amine hydrochloride
(II), HC1: R2 = H; R3 = -CH3; R4 = H; R5 = 4-Br; R6 = H;
R7 = H; R8 = 4-Cl; R9 = 2-Cl.
To a solution of 20 g of the compound obtained in
Preparation 3.1 in 200 ml of chloroform are added 7 g
of hexamethylenetetramine and the mixture is kept
stirring for 5 days at RT. 50 ml of ether are then


added, the precipitate formed is drained and dried. The
precipitate is taken up in 50 ml of EtOH, 15 ml of
concentrated HCl are added and the mixture is heated at
50°C for 5 hours. The white insoluble matter is
filtered and the filtrate is concentrated under vacuum.
The residue is taken up in ether, the organic phase is
washed with 50 ml of 5N NaOH, dried over Na2SO4 and the
solvent is evaporated under vacuum. The residue is
taken up in a 2N hydrochloric ether solution, the
precipitate formed is drained, washed with ether and
dried. 14.37 g of the expected product are obtained.
Preparation 4.2
[[5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]amine hydrochloride
(II), HCl: R2 = H; R3 = -CH3; R4 = H; R5 = 4-Cl; R6 = H;
R7 = H; R8 = 4-Cl; R9 = 2-C1.
This compound is prepared according to the procedure
described in Preparation 4.1 from 25 g of the compound
obtained in Preparation 3.2 in 150 ml of chloroform,
9 g of hexamethylenetetramine, 100 ml of ether, 250 ml
of EtOH and 30 ml of concentrated HCl. 24 g of the
expected product are obtained.
Preparation 4.3
[[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl] methylamine hydrochloride
(II), HCl: R2 = H; R3 = -CH2CH3; R4 = H; R5 = 4-Br;
R6 = H; R7 = H; R8 = 4-Cl; R9 = 2-C1.
To a solution of 9 g of the compound obtained in
Preparation 3.3 in 100 ml of chloroform are added 2.9 g
of hexamethylenetetramine and the mixture is kept
stirring for 10 days at RT. 50 ml of ether are then
added, the mixture is kept stirring for 10 minutes, the
reaction mixture is concentrated by half under vacuum,
50 ml of ether are added and the precipitate formed is
drained. The precipitate is taken up in 50 ml of EtOH,
15 ml of concentrated HCl are added and the mixture is
heated under reflux for 2 hours. The white insoluble

matter is filtered and the filtrate is concentrated
under vacuum. The residue is extracted with ether, the
organic phase is washed with 20 ml of 1N NaOH, with a
saturated NaCl solution, dried over Na2SO4 and the
solvent is evaporated under vacuum. The residue is
taken up in a 2N hydrochloric ether solution and the
precipitate formed is drained. 8.5 g of the expected
product are obtained.
By following the procedures described in Preparations 4
above, the compounds of formula (II) assembled in
TABLE IV below are prepared.

5. Preparations of the compounds of formula (III)
Cyclohexanesulfonyl chloride



A mixture of 25 g of cyclohexanethiol in 83 ml of
acetic acid and 4 ml of water is cooled to 0°C, and
then chlorine gas is bubbled through until the yellow
color persists. The reaction mixture is poured into
water, extracted three times with ether, the combined
organic phases are washed twice with water, dried over
Na2SO4 and the solvent is evaporated under vacuum. The
residue is distilled at a pressure of 4 Pa and 13.3 g
of the expected product are obtained, b.p. = 154°C.
EXAMPLE 1: Compound No. 8
N-[[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-methy1-
1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)benzene-
sulfonamide
(I) : R1 = R2 = H; R3 = -CH3; R4 = H;
R5 = 4-Br; R6 = H; R7 = H; R8 = 4-Cl; R9 = 2-Cl
To a solution of 0.7 g of the compound obtained in
Preparation 4.1 in 20 ml of DCM is added 0.42 ml of
triethylamine, followed dropwise by 0.39 g of 4-
(trifluoromethyl)benzenesulfonyl chloride and the
mixture is kept stirring overnight at RT. 10 ml of
water are added and the mixture is kept stirring for 10
minutes. After decantation, the organic phase is washed
twice with a saturated NaHCO3 solution, twice with a
buffer solution pH = 2, twice with a saturated NaCl
solution, dried over Na2SO4 and the solvent is
evaporated under vacuum. The product obtained is
crystallized from a cyclohexane/AcOEt mixture (95/5;
v/v). 0.75 g of the expected product is obtained,
m.p. = 195°C.
1H NMR: DMSO-d6: δ (ppm): 1.95: s: 3H; 4.15: s: 2H; 7.0:
d: 2H; 7.2-8.1: m: 9H; 8.5: s: 1H.
EXAMPLE 2: Compound No. 28

N- [ [5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-
1H-pyrazol-3-yl]methyl]-3-chlorobenzenesulfonamide
(I): R1 = ; R2 = H; R3 = -CH2CH3; R4 = H;
R5 = 4-Br; R6 = H; R7 = H; R8 = 4-Cl; R9 = 2-Cl
To a solution of 0.7 g of the compound obtained in
Preparation 4.3 in 30 ml of DCM are added 0.4 ml of
triethylamine, followed dropwise by 0.32 g of 3-
chlorobenzenesulfonyl chloride and the mixture is kept
stirring overnight at RT. The reaction mixture is
concentrated under vacuum, the residue is extracted
with AcOEt, the organic phase is washed twice with a
saturated NaHCO3 solution, twice with a buffer solution
pH = 2, twice with a saturated NaCl solution, dried
over Na2SO4 and the solvent is evaporated under vacuum.
The residue is chromatographed on silica gel, eluting
with the cyclohexane/AcOEt mixture from (90/10; v/v) to
(75/25; v/v). The product obtained is taken up in
1.5 ml of AcOEt, cyclohexane is added, the precipitate
formed is drained and dried. 0.31 g of the expected
product is obtained, m.p. = 169°C.
1H NMR: DMSO-d6: δ (ppm) : 1.0: t: 3H; 2.4: q: 2H; 4.15:
s: 2H; 7.0: d: 2H; 7.2-7.9: m: 9H; 8.4: s: 1H.
EXAMPLE 3: Compound No. 42
N-[[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-
1H-pyrazol-3-yl]methyl]-1-[3-(trifluoromethyl)phenyl]-
methanesulfonamide
(I) : R1 R2 = H; R3 = -CH2CH3; R4 = H;
R5 = 4-Br; R6 = H; R7 = H; R8 = 4-Cl; R9 = 2-Cl
To a solution of 0.5 g of the compound obtained in
Preparation 4.3 in 25 ml of DCM is added 0.3 ml of
triethylamine, followed by 0.28 g of [3-
(trifluoromethyl)phenyl]methanesulfonyl chloride and
the mixture is kept stirring overnight at RT. The

reaction mixture is concentrated under vacuum, the
residue is taken up in water, extracted with AcOEt, the
organic phase is washed with a saturated NaHCO3
solution, with a buffer solution pH = 2, with a
saturated NaCl solution, dried over Na2SO4 and the
solvent is evaporated under vacuum. The residue is
chromatographed on silica gel, eluting with the
cyclohexane/AcOEt mixture from (90/10; v/v) to (85/15;
v/v). 0.3 g of the expected compound is obtained,
m.p. = 108°C.
1H NMR: DMSO-d6: δ (ppm) : 1.03: t: 3H; 2.5: mt: 2H;
4.23: d: 2H; 4.5: s: 2H; 7.13: d: 2H; 7.4-7.75: m: 9H;
7.80: t: 1H.
EXAMPLE 4: Compound No. 7 3
N-[[5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-
1H-pyrazol-3-yl]methyl]-3-chloro-N-methylbenzene-
sulfonamide
(I) : R1 = ; R2 = CH3; R3 = -CH2CH3; R4 = H;
R5 = 4-Br; R6 = H; R7 = H; R8 = 4-Cl; R9 = 2-C1
To a mixture of 0.41 g of compound No. 28 and 0.1 g of
K2CO3 in 34 ml of DMF is added 0.05 ml of methyl iodide,
followed by heating under reflux for 2 hours and the
mixture is kept stirring overnight at RT. The reaction
mixture is concentrated under vacuum, the residue is
taken up in water, extracted with DCM, the organic
phase is washed with a buffer solution of pH = 2, with
a saturated NaHCO3 solution, with a saturated NaCl
solution, dried over Na2SO4 and the solvent is
evaporated under vacuum. The residue is chromatographed
on silica gel, eluting with the cyclohexane/AcOEt
mixture from (90/10; v/v) to (80/20; v/v). 0.263 g of
the expected compound is obtained after drying under
vacuum, m.p. = 78°C.
The table which follows illustrates the chemical
structures and the physical properties of some examples

of compounds according to the invention. In this table:
in the "salt" column "-" represents a compound
in the form of a free base, while "HCl"
represents a compound in hydrochloride form;
in the column "method" represents one of the
analytical methods used to determine the
molecular peak MH+ and the retention time as
described above.





















(a) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.1 and the corresponding compound of
formula (III) .
(b) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.2 and the corresponding compound of
formula (III) .
(c) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.3 and the corresponding compound of
formula (III) .
(d) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.4 and the corresponding compound of
formula (III) .
(e) Compound prepared according to the procedure

described in Example 1 from the compound obtained in
Preparation 4.5 and the corresponding compound of
formula (III) .
(f) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.6 and the corresponding compound of
formula (III) .
(g) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.7 and the corresponding compound of
formula (III) .
(h) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.8 and the corresponding compound of
formula (III) .
(i) Compound prepared according to the procedure
described in Example 1 from the compound obtained in
Preparation 4.9 and the corresponding compound of
formula (III) .
The compounds of formula (I) possess a very good
affinity in vitro (IC50 ≤ 5x10-7M) for the CB1
cannabinoid receptors, under the experimental
conditions described by M. Rinaldi-Carmona et al. (FEBS
Letters, 1994, 350, 240-244).
The antagonist nature of the compounds of formula (I)
has been demonstrated by the results obtained in the
adenylate-cyclase inhibition models as described in
M. Bouaboula et al. , J. Biol. Chem., 1995, 270, 13973-
13980, M. Rinaldi-Carmona et al., J. Pharmacol. Exp.
Ther., 1996, 278, 871-878 and M. Bouaboula et al., J.
Biol. Chem., 1997, 222., 22330-22339.
The toxicity of the compounds of formula (I) is
compatible with their use as a medicament.
Thus, according to another of its aspects, the subject
of the invention is medicaments which comprise a


compound of formula (I), or an addition salt of the
latter with a pharmaceutically acceptable acid, or
alternatively a solvate or a hydrate of the compound of
formula (I) .
Thus, the compounds according to the invention may be
used in humans or animals, in the treatment or the
prevention of diseases involving the CB1 cannabinoid
receptors.
For example and without limitation, the compounds of
formula (I) are useful as psychotropic medicaments, in
particular for the treatment of psychiatric disorders
including anxiety, depression, mood disorders,
insomnia, delirium disorders, obsessive disorders,
psychoses in general, schizophrenia, attention deficit
hyperactivity disorder (ADHD), in particular in
hyperkinetic children (MBD), and for the treatment of
disorders linked to the use of psychotropic substances,
in particular in the case of a substance abuse and/or
of dependence on a substance, including alcohol
dependence and nicotine dependence.
The compounds of formula (I) according to the invention
may be used as medicaments for the treatment of
migraine, stress, diseases of psychosomatic origin,
panic attacks, epileptic attacks, motion disorders, in
particular dyskinesia or Parkinson's disease, tremors
and dystonia.
The compounds of formula (I) according to the invention
may also be used as medicaments in the treatment of
memory disorders, cognitive disorders, in particular in
the treatment of senile dementia, Alzheimer's disease,
and in the treatment of attention or vigilance
disorders. Furthermore, the compounds of formula (I)
may be useful as neuroprotectants, in the treatment of
ischemia, cranial traumas and the treatment of
neurodegenerative diseases: including chorea,


Huntington's chorea, Tourrette's syndrome.
The compounds of formula (I) according to the invention
may be used as medicaments in the treatment of pain:
neuropathic pain, acute peripheral pain, chronic pain
of inflammatory origin.
The compounds of formula (I) according to the invention
may be used as medicaments in the treatment of appetite
disorders, craving disorders (for sugars,
carbohydrates, drugs, alcohol or any appetizing
substance) and/or alimentary canal disorders, in
particular for the treatment of obesity or of bulimia
and for the treatment of type II diabetes or non-
insulin-dependent diabetes and for the treatment of
dyslipidaemia and of metabolic syndrome. Thus, the
compounds of formula (I) according to the invention are
useful in the treatment of obesity and of the risks
associated with obesity, in particular cardiovascular
risks. Furthermore, the compounds of formula (I)
according to the invention may be used as medicaments
in the treatment of gastrointestinal disorders,
diarrhoeal disorders, ulcers, emesis, bladder and
urinary disorders, disorders of endocrine origin,
cardiovascular disorders, hypotension, hemorrhagic
shock, septic shock, chronic cirrhosis of the liver,
hepatic steatosis, steatohepatitis, asthma, Raynaud's
syndrome, glaucoma, fertility disorders, inflammatory
phenomena, immune system diseases, in particular
autoimmune and neuroinflammatory diseases such as
rheumatoid arthritis, reactive arthritis, diseases
causing demyelinization, multiple sclerosis, infectious
and viral diseases such as encephalitis, stroke and as
medicaments for anticancer therapy, for the treatment
of Guillain-Barre syndrome and for the treatment of
osteoporosis.
According to the present invention, the compounds of
formula (I) are most particularly useful for the


treatment of psychotic disorders, in particular
schizophrenia, attention deficit hyperactivity
disorders (ADHD), in hyperkinetic children (MBD); for
the treatment of appetite disorders and obesity; for
the treatment of memory and cognitive disorders; for
the treatment of alcohol dependence, nicotine
dependence, that is to say for withdrawal from alcohol
and for smoking cessation.
According to one of its aspects, the present invention
relates to the use of a compound of formula (I), of its
pharmaceutically acceptable salts and of their solvates
or hydrates for the treatment of the disorders and
diseases indicated above.
According to another of its aspects, the present
invention relates to pharmaceutical compositions
comprising, as active ingredient, a compound according
to the invention. These pharmaceutical compositions
contain an effective dose of at least one compound
according to the invention, or a pharmaceutically
acceptable salt, a solvate or a hydrate of the said
compound, and at least one pharmaceutically acceptable
excipient.
The said excipients are chosen according to the
pharmaceutical dosage form and the desired mode of
administration, from the usual excipients which are
known to a person skilled in the art.
In the pharmaceutical compositions of the present
invention for oral, sublingual, subcutaneous,
intramuscular, intravenous, topical, local,
intratracheal, intranasal, transdermal or rectal
administration, the active ingredient of formula (I)
above, or its possible salt, solvate or hydrate, may be
administered in unit form for administration, as a
mixture with conventional pharmaceutical excipients, to
animals and to human beings for the prophylaxis or the

treatment of the disorders or diseases above.
The appropriate unit forms for administration comprise
the forms by the oral route such as tablets, soft or
hard gelatin capsules, powders, granules and oral
solutions or suspensions, the forms for sublingual,
buccal, intratracheal, intraocular or intranasal
administration, for administration by inhalation, the
forms for topical, transdermal, subcutaneous,
intramuscular or intravenous administration, the forms
for rectal administration and implants. For topical
application, it is possible to use the compounds
according to the invention in creams, gels, ointments
or lotions.
By way of example, a unit form for administration of a
compound according to the invention in tablet form may
comprise the following compounds:
Compound according to the invention : 50.0 mg
Mannitol : 223.75 mg
Croscarmellose sodium : 6.0 mg
Maize starch : 15.0 mg
Hydroxypropylmethylcellulose : 2.25 mg
Magnesium stearate : 3.0 mg
By the oral route, the dose of active ingredient
administered per day may be up to 0.01 to 100 mg/kg, in
single or divided doses, preferably 0.02 to 50 mg/kg.
There may be specific cases where higher or lower doses
are appropriate, such doses do not depart from the
scope of the invention. According to the usual
practice, the appropriate dose for each patient is
determined by the doctor according to the mode of
administration, the weight and the response of the said
patient.
The present invention, according to another of its

aspects, also relates to a method for treating the
pathologies indicated above, which comprises the
administration, to a patient, of an effective dose of a
compound according to the invention, or one of its
pharmaceutically acceptable salts or hydrates or
solvates.

WE CLAIM
1. A compound corresponding to formula (I):

in which:
R1 represents
• a (C1-C6)alkyl;
• a (C3-C7) cycloalkyl which is unsubstituted or
substituted once or several times with a
(C1-C3)alkyl group;
• a (C3-C7) cycloalkylmethyl which is unsubstituted
or substituted once or several times on the
carbocycle with a (C1-C3) alkyl;
• a phenyl which is unsubstituted or mono-,
di- or trisubstituted with a substituent
independently chosen from a halogen atom, a
(C1-C4) alkyl, a (C1-C3) alkoxy, a cyano, a
trifluoromethyl radical, a trifluoromethoxy
radical, an S(O)nAlk group, a (C1-C3)
alkylcarbonyl group, a phenyl;
• a benzyl which is unsubstituted or mono- or
disubstituted with a substituent
independently chosen from a halogen atom, a
(C1-C3) alkyl, a (C1-C3) alkoxy; a
trifluoromethyl radical;
• a thienyl which is unsubstituted or substituted
with a halogen atom or with an isoxazolyl;
R2 represents a hydrogen atom or a (C1-C3) alkyl;
R3 represents a hydrogen atom or a (C1-C5) alkyl;

R4, R5, R6, R7, R8 and R9 each independently
represent a hydrogen atom, a halogen atom, a
(C1-C7) alkyl, a (C1-C5) alkoxy, a trifluoromethyl
radical or an S(O)nAlk group;
n represents 0, i or 2;
Alk represents a (C1-C4) alkyl,
in the form of a base or an addition salt with an
acid, and in the form of a hydrate or a solvate.
2. The compound of formula (I) as claimed in claim 1,
in which:
R1 represents
• an ethyl, an isopropyl, an n-butyl;
• a cyclohexyl;
• a cyclohexylmethyl;
• a 2-chlorophenyl, a 3-chlorophenyl, a 2-
fluorophenyl, a 3-chloro-4-fluorophenyl, a
4-bromo-2-ethylphenyl, a 3-methylphenyl, a
4-tert-butylphenyl, a 3,5-dimethylphenyl, a
3-methoxyphenyl, a 4-methoxyphenyl, a 3-
cyanophenyl, a 4-cyanophenyl, a 2-
(trifluoromethyl)phenyl, a 3-
(trifluoromethyl)phenyl, a 4-(trifluoro-
methyl) phenyl, a 3, 5-bis(trifluoromethyl)-
phenyl, a 2-(trifluoromethoxy)phenyl, a 3-
(trifluoromethoxy)phenyl, a 2-
(methylsulfonyl)phenyl, a 3-
(methylsulfonyl)phenyl, a 3-acetylphenyl, a
3-biphenyl, a 2-biphenyl;
• a 3-chlorobenzyl, a 2-fluorobenzyl, a 4-
fluorobenzyl, a 3-(trifluoromethyl)benzyl, a
4-(trifluoromethyl)benzyl;
• a 5-bromo-2-thienyl; a 5-isoxazol-3-yl-2-
thienyl;
R2 represents a hydrogen atom or a methyl;
R3 represents a methyl or an ethyl;
R4 represents a hydrogen atom;
R5 is at the 4-position of the phenyl and

represents a bromine, chlorine or fluorine atom,
or a methoxy;
R6 represents a hydrogen atom;
R7 represents a hydrogen atom;
R8 is at the 4-position of the phenyl and
represents a hydrogen atom, a chlorine atom, a
fluorine atom;
R9 is at the 2-position of the phenyl and
represents a chlorine or fluorine atom;
in the form of a base or of an addition salt with
an acid, and in the form of a hydrate or a
solvate.
3. The compound of formula (I) as claimed in claim 1,
chosen from:
N- [ [5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-ltf-pyrazol-3-yl]methyl]butane-1-
sulfonamide;
N- [ [5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-
cyclohexanesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-
cyclohexylmethanesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
chlorobenzenesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-4-tert-
butylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
- N-[[5-(4-bromophenyl)=1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-4-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)

benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-2-(methylsulfonyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichiorophenyi)-4-
methyl-1H-pyrazol-3-yl]methyl]-1-(3-chlorophenyl)
methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl] -1- [3-
(trifluoromethyl)phenyl]methanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-chloro-4-
fluorobenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-butane-1-
sulfonamide;
- 3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
- 4-tert-butyl-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-4-
(trifluoromethyl)benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl] -2-
(trifluoromethoxy)benzenesulfonamide;
N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-2-
(methylsulfonyl)benzenesulfonamide;
- 3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-

dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-
4-fluorobenzenesulfonamide;
4-bromo-N-[[5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-
2 —ethylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]ethanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]propane-2-
sulfonamide;
N-[[5-(4-bromophenyl)-1-(2, 4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]butane-1-sulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-
cyclohexanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-
cyclohexylmethanesulfonamide;
N-[[5-(4-bromophenyl)-1-(2, 4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-
chlorobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2, 4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-2-
chlorobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-lif-pyrazol-3-yl] methyl] -3-
methylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-tert-
butylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-
methoxybenzenesulfonamide;


ethyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)

benzenesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl] -3- (trif luoromethyl)
benzenesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethyl)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3-(trifluoromethoxy)
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethoxy)
benzenesulfonamide;
3-acetyl-N-[[5-(4-bromophenyl)-1-(2,4-
dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
e thyl-1H-pyr a zol-3-yl] methyl ]bipheny 1-3-
sulfonamide;
- N-[[5-(4-bromophenyl)-1-(2, 4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-[4-
(trifluoromethyl)phenyl]methanesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-[3-
(trifluoromethyl)phenyl]methanesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3,5-
dimethylbenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2, 4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-3,5-bis
(trifluoromethyl)benzenesulfonamide;
- 3-chloro-N-[[1-(2-chlorophenyl)-5-(4-
chlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]
benzenesulfonamide;
N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-2-
fluorobenzenesulfonamide;
N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-

methyl-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[ [1- (2-chlorophenyl)-5-(4-chlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
- N-[ [5- (4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
methoxybenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazol-3-yl]methyl]-3-
cyanobenzenesulfonamide;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-l-(2-
fluorophenyl)methanesulfonamide;
- N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl]-1-(4-
fluorophenyl)methanesulfonamide;
5-bromo-N-[[5-(4-bromophenyl)-1-(2,4-
dichlorophenyl)-4-ethyl-1H-pyrazol-3-
yl]methyl]thiophene-2-sulfonamide ;
N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-
ethyl-1H-pyrazol-3-yl]methyl] -5-isoxazol-3-
ylthiophene-2-sulfonamide;
- 3-chloro-N-[[1-(2,4-dichlorophenyl)-5- (4-
methoxyphenyl)-4-methyl-1H-pyrazol-3-
yl]methyl]benzenesulfonamide;
- N-[[1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-
4-methyl-1H-pyrazol-3-yl]methyl]-3-
methylbenzenesulfonamide;
in the form of a base or of an addition salt with
an acid, and in the form of a hydrate or of a
solvate.
4. A method for preparing the compounds of formula
(I) as claimed in claim 1, wherein,
a compound of formula:


in which R2, R3, R4, R5, R6, R7, R8 and R9 are as
defined for a compound of formula (I) in claim 1,
is reacted, in the presence of a base and in a
solvent, with a sulfonyl halide of formula:

in which R1 is as defined for a compound of formula
(I) in claim 1 and Hal represents a halogen atom.
5. A medicament, wherein it comprises a compound of
formula (I) as claimed in any one of claims 1 to
3, or an addition salt of this compound with a
pharmaceutically acceptable acid, or a hydrate or
a solvate of the compound of formula (I).
6. A pharmaceutical composition, wherein it comprises
a compound of formula (I) as claimed in any one of
claims 1 to 3, or a pharmaceutically acceptable
salt, a hydrate or a solvate of this compound, and
at least one pharmaceutically acceptable
excipient.

7. A compound of formula (I) as claimed in any one of
claims 1 to 3 for the preparation of a medicament
intended for the treatment and prevention of
appetite disorders, gastrointestinal disorders,
inflammatory phenomena, immune system diseases,
psychotic disorders, alcohol dependence and
nicotine dependence.


The invention relates to compounds of formula (I):

Wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 are as defined herein. The
invention also relates to the preparation method thereof and to the use
of same in therapeutics.

Documents:

01885-kolnp-2006 abstract.pdf

01885-kolnp-2006 assignment.pdf

01885-kolnp-2006 claims.pdf

01885-kolnp-2006 correspondence others.pdf

01885-kolnp-2006 description(complete).pdf

01885-kolnp-2006 form-1.pdf

01885-kolnp-2006 form-3.pdf

01885-kolnp-2006 form-5.pdf

01885-kolnp-2006 international publication.pdf

01885-kolnp-2006 international search authority report.pdf

01885-kolnp-2006-correspondence others-1.1.pdf

01885-kolnp-2006-correspondence-1.2.pdf

01885-kolnp-2006-form-18.pdf

01885-kolnp-2006-form-3-1.1.pdf

01885-kolnp-2006-pct other.pdf

1880-kolnp-2006-form 13.pdf

1885-KOLNP-2006-ABSTRACT.pdf

1885-KOLNP-2006-ASSIGNMENT 1.1.pdf

1885-kolnp-2006-assignment 1.2.pdf

1885-KOLNP-2006-CANCELLED PAGES.pdf

1885-KOLNP-2006-CLAIMS.pdf

1885-KOLNP-2006-CORRESPONDENCE 1.1.pdf

1885-kolnp-2006-correspondence 1.2.pdf

1885-KOLNP-2006-DESCRIPTION (COMPLETE).pdf

1885-kolnp-2006-examination report 1.2.pdf

1885-KOLNP-2006-FORM 1.pdf

1885-kolnp-2006-form 18 1.2.pdf

1885-kolnp-2006-form 3 1.2.pdf

1885-KOLNP-2006-FORM 3.1.1.pdf

1885-KOLNP-2006-FORM 3.pdf

1885-kolnp-2006-form 5 1.2.pdf

1885-kolnp-2006-gpa 1.2.pdf

1885-kolnp-2006-granted-abstract.pdf

1885-kolnp-2006-granted-claims.pdf

1885-kolnp-2006-granted-description (complete).pdf

1885-kolnp-2006-granted-form 1.pdf

1885-kolnp-2006-granted-specification.pdf

1885-kolnp-2006-others 1.2.pdf

1885-KOLNP-2006-OTHERS.pdf

1885-KOLNP-2006-PETITION UNDER RULE 137.pdf

1885-kolnp-2006-reply to examination report 1.2.pdf

1885-KOLNP-2006-REPLY TO EXAMINATION REPORT.pdf

1885-kolnp-2006-translated copy of priority document 1.2.pdf

abstract-01885-kolnp-2006.jpg


Patent Number 247116
Indian Patent Application Number 1885/KOLNP/2006
PG Journal Number 13/2011
Publication Date 01-Apr-2011
Grant Date 28-Mar-2011
Date of Filing 06-Jul-2006
Name of Patentee SANOFI-AVENTIS
Applicant Address 174, AVENUE DE FRANCE F-75013 PARIS FRANCE
Inventors:
# Inventor's Name Inventor's Address
1 BARTH FRANCIS 5, ALLEE DES TERRES ROUGES F-34680 SAINT GEORGES D'ORQUES FRANCE
2 MARTINEZ SERGE 4 RUE RAOUL F-3400 MONTPELLIER FRANCE
3 RINALDI-CARMONA MURIELLE 2 RUE DE FONTARDIES F-34680 SAINT GEORGES D'ORQUES FRANCE
4 CONGY CHRISTIAN 58, ALLEE DE LA MARQUISE F-34980 SAINT GELY DU FESC FRANCE
PCT International Classification Number C07D 231/12
PCT International Application Number PCT/FR2005/000031
PCT International Filing date 2005-01-07
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 0400257 2004-01-12 France