Title of Invention

ESTER COMPOUND AND MEDICAL USE THEREOF

Abstract A novel therapeutic agent for hyperlipidemia, which is as ester compound represented by the formula (1") (wherein R1 and R2 are each hydrogen atom or optionally substituted aryl, etc.; X is - COO- or -CON (R10)-; R3 and R4 are each hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy, etc.; R5 and R6 are each hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy, etc; R8 and R9 are each independently hydrogen atom, C1-C6 alkyl -CON (R18) (R19) Of - COO (R20 ), etc.; ring A, ring B and ring C are each independently aryl or heterocycle residue, etc.; Alk1 and Alk2 are each independently alkanediyl, etc.; 1 and m are each an integer of 0 or 1 to 3) or a prodrug thereof, or a pharmaceutically acceptable salt of either. The therapeutic agent selectively inhibits MTP in the small intestine, thus causes no such side effect as a fatty liver.
Full Text DESCRIPTION
ESTER COMPOUND AND MEDICAL USE THEREOF
Technical Field
The present invention relates to a novel ester compound,
and also relates to a pharmaceutical composition comprising a
novel ester compound which selectively inhibits microspmal
triglyceride transfer protein (MTP) in the small intestine or
a prodrug thereof, or a pharmaceutically acceptable salt of
either. Further, the present invention relates to an agent for
the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension comprising a novel ester compound which
selectively inhibits MTP in the small intestine or a prodrug
thereof, or a pharmaceutically acceptable salt of either as an
active ingredient. In addition, the present invention relates
to an agent for the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension, which has a novel function that has never been
known before.
Background Art
It has been said that hyperlipidemia, diabetes,
hypertension or the like is one of the risk factors for
arteriosclerosis. Hyperlipidemia is a condition where the
concentration of lipid such as cholesterol is abnormally
elevated in the blood. Types of hyperlipidemia, depending on
the cause, include primary hyperlipidemia caused by genetic
abnormality in enzyme, protein, lipoprotein and the like which
participate in the metabolism of low-density lipoprotein (LDL) ,
secondary hyperlipidemia due to various disease or drug
administration, and acquired hyperlipidemia basically
resulting from overnutrition.
Meanwhile, lipid taken in from food is absorbed in the
small intestine by the action of bile acid, and secreted as
chylomicron in the blood via lymphatic vessels. The
triglyceride moiety of the secreted chylomicrons is hydrolyzed
to free fatty acids by the action of lipoprotein lipase (LPL)
existing in capillary vessels to become chylomicron remnants
having a high content of cholesteryl ester (CE), which is then
absorbed in the liver by the mediation of chylomicron remnant
receptor in the liver. Further, in the liver, the absorbed
chylomicron remnant and free fatty acid are converted to CE and
TG, respectively, which are then associated with apolipoprotein
B synthesized on rough surfaced endoplasmic reticulum to form
very low density lipoprotein (VLDL). The VLDL is transferred
to the Golgi apparatus, modified and secreted outside cells,
and it becomes intermediate density lipoprotein (IDL) by the
action of LPL. The IDL is converted to LDL by the action of
hepatic triglyceride lipase (HTGL), and lipids are distributed
to peripheral tissues.
It has long been indicated that, during the
above-mentioned formation of chylomicron in the small intestine
or VLDL in the liver, a protein having TG- or CE-transfer
activity is existing in microsomal fractions of the small
intestine or liver. Meanwhile, the protein, i.e. MTP
(microsomal triglyceride transfer protein) was purified and
separated from microsomal fractions of bovine liver by Wetterau
et al. in 1985 (Wetterau J.R. et al: Chem.Phys .Lipids 38,
205-222(1985)). MTP, however, began attracting a lot of
attention in the field of clinical medicine only after it was
reported in 1993 that the cause of abetalipoproteinemia lay in
the deficit of MTP. In other word, the disease is characterized
in that, while the genes related to apolipoprotein B are normal,
apolipoprotein B is hardly detected in the serum, the level of
serum cholesterol is 50mg/dL or lower, the level of serum
triglyceride is extremely low and, moreover, lipoproteins
including apolipoprotein B such as chylomicron, VLDL, LDL, etc.
do not at all exist in the blood. By this finding, it has been
shown that MTP is an integral protein involved in the
association between apolipoprotein B and TG or CE, i.e. the
formation of VLDL or chylomicron, and plays an essential role
in secretion thereof.
Since lipid is by nature insoluble in water, lipid in the
blood is combined with a hydrophilic protein known as
apolipoprotein and exists as so-called lipoprotein. All the
VLDL, IDL, LDL or chylomicron, etc. related to hyperlipidemia
are a lipoprotein.
MTP exists in the microsome fractions of hepatocytes and
intestinal epithelial cells, and catalyses the transfer of TG
or CE in cells. In the liver and small intestine, along with
the synthesis of apolipoprotein (apolipoprotein B100 in the
liver and apolipoprotein B48 in the small intestine), TG and
CE are combined with respective apolipoprotein B by the transfer
activity of MTP, and thus VLDL or chylomicron is formed. As
a result, those lipoproteins are secreted outside the cells as
VLDL in the liver or as chylomicron in the small intestine. It
should be said that MTP is indispensable for the construction
of those lipoproteins. Namely, if the activity of MTP is
blocked, the transfer of lipid such as TG and CE, etc. to
apolipoprotein is inhibited, whereby formation of a lipoprotein
can be inhibited.
On the other hand, it has been elucidated that LDL in
general is closely related to the progression of
arteriosclerosis. That is, LDL permeating endothelium of
blood vessels is deposited in intercellular matrix of vessel
wall, where oxidative denaturation takes place and lipid
peroxides or denaturated proteins induce a series of
inflammation reactions. Consequently, macrophage invasion,
leading to lipid deposit or foaming cells, migration or
proliferation of smooth muscle cells and increase in
intercellular matrix, etc. take place, which leads to the
development of arteriosclerosis plaque. On the basis of the
above, it is supposed to be possible to prevent or treat
arteriosclerosis, coronary artery diseases or hypertension by
reducing the level of LDL.
As already mentioned, it is possible to inhibit the
formation of lipoprotein such as chylomicron, VLDL, LDL, etc.
by inhibiting the action of MTP. Accordingly, it has been
expected that it should become possible to control lipoprotein
such as TG, cholesterol and LDL, etc. in blood and to control
lipid in cells by adjusting the activity of MTP, and therefore,
a novel agent for the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, diabetes, obesity,
or hypertension, and further, an agent for the treatment or
prophylaxis of pancreatitis, hypercholesterolemia,
hyperglyceridemia, etc. has been expected to be provided.
However, with the development of MTP inhibitors, some
cases of fatty liver were reported and concern over
hepatotoxicity has been raised.
For these reasons, a novel MTP inhibitor causing no side
effect such as a fatty liver, etc. has been strongly desired.
In the conventional manners, combined therapies of
various combinations of different antihyperlipidemic drugs
have been tried. However, when, for example, a statin-type drug
and a resin-type drtfg are given together, undesirable side
effects such as increased GTO and GPT, constipation, blocking
of absorption of vitamin A, D, E and K and the like are observed.
On the other hand, when a statin-type drug and a fibrate drug
are given together, side effects such as rhabdomyolysis or
increased CPK (creative phosphokinase) are observed. Thus,
with regard to a combined therapy for hyperlipidemia, a
medicament for a combined administration which can be
administered in combination with a conventional
antihyperlipidemic drug without causing any above-mentioned
side effect has been desired.
Meanwhile, examples of the known compound having MTP
inhibitory activity with a similar structure of the compounds
of the present invention are described below.
The following compound is disclosed in WO97/26240.
The following compound is disclosed in WO97/43257.
The following compound is disclosed in WO98/23593.
The following compound is disclosed in WO99/63929.
The following compound is disclosed in WO2000/5201.
The following compound is disclosed in J. Med.
Chem.(2001), 44(6) p.851-856.
The following compound is disclosed in EP 1099701.
The following compound is disclosed in WO2001/77077.
The following compound is disclosed in J. Med.
Chem.(2001), 44(6) p.4677-4687.
The following compound is disclosed in WO2002/4403.
In the above literatures, however, there is no disclosure
of a compound comprising ester as the essential structure as
that disclosed in the present invention, much less the
disclosure of the data indicating that when a compound has the
structure disclosed in the present invention, the compound
selectively inhibits MTP in the small intestine while rarely
affects MTP in the liver.
Disclosure of the Invention
Although the development of new antihyperlipidemic drugs
working due to its MTP inhibitory activity has been advanced
nowadays, those drugs are not satisfactory in terms of the level
of action and the accompanying side effect such as a fatty liver,
etc. Thus, the development of an antihyperlipidemic drug
causing no side effect against the liver that is seen in the
case of conventional MTP inhibitors and also having excellent
MTP inhibitory activity has been strongly desired.
The inventors and those involved in the present invention
have carried out intensive studies to provide a novel MTP
inhibitor causing no above-mentioned side effect such as a fatty
liver. As a result, they have found that an MTP inhibitor, which
selectively inhibits MTP in the small intestine but
substantially does not inhibit MTP in the liver, significantly
lowers the level of unnecessary TG or cholesterol without
causing a side effect such as a fatty liver etc. Surprisingly,
they have also found that the compound having ester structure
represented by the below-mentioned formula (1) is immediately
metabolized in the small intestine, blood or liver, which makes
it possible for the compound to selectively affect MTP in the
small intestine without substantially inhibiting MTP in the
liver.
To be more specific, according to the conventional drug
design concept for the preparation of a prodrug, the carboxylic
acid which is the active principle is esterif ied to improve the
absorption rate in the small intestine and is immediately
metabolized in blood to reproduce carboxylic acid which is the
active principle . On the other hand, a drug design concept that
is different from the above concept for the preparation of a
prodrug is used in the present invention. Namely, by
introducing at least one ester in a molecular body of a compound
having MTP inhibitory activity, the compound is , after it exerts
MTP inhibitory activity on mucous membranes of the small
intestine, immediately metabolized by an esterase or a
metabolic enzyme, etc. in the small intestine, portal (blood)
and liver to be transformed to corresponding carboxylic acid
and alcohol which do not have MTP inhibitory activity. This
is completely a new concept, by means of which MTP in the liver
is not substantially affected and MTP in the small intestine
is selectively inhibited. Further, the compounds of the
present invention show strong MTP inhibitory activity in vitro,
thus potently inhibit MTP in the small intestine and
significantly lower triglyceride and cholesterol in blood. In
addition, the compounds of the present invention significantly
lower non-HDL cholesterol and, surprisingly, increase plasma
HDL cholesterol.
Accordingly, the inventors of the present invention have
found that when a compound comprises the ester structure
represented by the below-mentioned formula (1), the compound
is immediately metabolized in the small intestine, blood or
liver after it strongly inhibits MTP in the small intestine and
hence MTP in the liver is not substantially inhibited, whereby
they have completed the present invention.
Thus, the present invention relates to
(1) An ester compound represented by the formula (1)

wherein
R1 and R2 are each hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl,
C1-C6 alkoxy, halo C1-C6 alkyl, halo C1-C6 alkyloxy, optionally
substituted C6-C14 aryl, optionally substituted C7-C16 aralkyl,
optionally substituted C6-C14 aryloxy, optionally substituted
C7-C16 aralkyloxy, optionally substituted C7-C15 arylcarbonyl,
optionally substituted heterocycle, C2-C7 alkoxycarbonyl,
halogen, C2-C6 alkenyl, -N(R40)(R41) wherein R40 and R41 are each
independently hydrogen or optionally substituted C6-C14 aryl;
ring A is C6-C14 aryl, heterocycle, or
X is -COO-(CH2)n-, -CON(R10)-(CH2)n- or -N(R10 )-CO-(CH2 )n-
wherein R10 is hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl and n
is an integer of 0 to 3;
R3 and R4 are each independently hydrogen, hydroxy,
halogen, optionally substituted C1-C6 alkyl, C1-C6 alkoxy, halo
C1-C6 alkyl, C7-C16 aralkyloxy, C1-C6 acyl, optionally
substituted heterocycle, -CON(R11) (R12) (wherein R11 and R12 are
each independently hydrogen, C1-C6 alkyl, optionally
substituted C6-C14 aryl, optionally substituted C7-C16 aralkyl,
C1-C6 alkoxy, or R11 and R12 maybe taken together with the nitrogen
to which they are attached to form

, wherein p is an integer of 0 to 2 ), - (CH2 )q-N( R13) (R14) (wherein
R13 and R14 are each independently hydrogen, C1-C6 alkyl, C2-C-
alkoxycarbonyl, C1-C6 acyl, or R13 and R14 may be taken together
with the nitrogen to which they are attached to form

wherein p has the same meaning as defined above and q is an
integer of 0 to 3), or -CO(R15) (wherein R15 is hydroxy, C1-C6
alkoxy, optionally substituted C5-C14 aryloxy, optionally
substituted C7-C16 aralkyloxy or C1-C6 alkyl);
ring B is
, wherein K is an integer of 0 to 2 , or ring B may be taken together
with R3, R10 and the nitrogen bound to R10 to form
Alkl1 is alkanediyl or alkenediyl;
Alkl2 is alkanediyl or alkenediyl;
1 is an integer of 0 to 3;
m is an integer of 0 to 3;
D is C1-C6 alkyl, C2-C5 alkenyl, C2-C7 alkoxycarbonyl,
-N(R42)-CO(R43) (wherein R42 is hydrogen or C1-C6 alkyl and R43 is
C6-C14 aryl or C7-C16 aralkyl), or the group represented by the
following formula

(wherein R5, R6 and R7 are each independently hydrogen, C1-C6
alkyl, C1-C6 alkoxy, C2-C7 alkoxycarbonyl, carboxyl, halogen,
cyano, nitro, halo C1-C6 alkyl, C1-C6 acyl, hydroxy, amino,
optionally substituted C6-C14 aryl, or
-(CH2)r-CON(R16) (R17) (wherein R16 and R17 are each independently
hydrogen, C1-C6 alkyl or halo C1-C6 alkyl and r is an integer of
0 to 3);
ring C is C6-C14 aryl, C7-C15 arylcarbonylamino, C8-C1-
aralkylcarbonylamino, heterocycle residue, C3-C7 cycloalkyl or
C7-C16 aralkyl, or ring C may be taken together with R7 and R8
to form
and
R8 and R9 are each independently hydrogen, C1-C6 alkyl,
optionally substituted C6-C14 aryl, hydroxy C1-C6 alkyl,
-CON (R18) (R19) (wherein R18 and R19 are each independently
hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, halo C1-C6 alkyl, C2-C12
alkoxyalkyl or optionally substituted C6-C14 aryl) , -COO(R20) or
-(CH2)S-OCO(R20) (wherein R20 is hydrogen, C1-C6 alkyl or C3-C7
cycloalkyl; s is an integer of 0 to 3), -N(R21) (R22) (wherein R21
and R22 are each independently hydrogen, C1-C6 alkyl, C1-C6 acyl,
C1-C6 alkylsulfonyl, or R21 and R22 may be taken together with
the nitrogen to which they are attached to form
or
R8 and R9 may be taken together to form C3-C7 cycloalkyl,
or a prodrug thereof, or a pharmaceutically acceptable salt of
either;
(2) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), wherein D is C1-C6 alkyl, C2-C6 alkenyl, C2-C7
alkoxycarbonyl or -N(R42)-CO(R43) in which R42 and R43 each has
the same meaning as defined above;
(3) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), wherein D is the group represented by the formula
in which R5, R6 and R7 each has the same meaning as defined above;
(4) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (3), wherein the ring C is

,in which q is an integer of 0 to 3 ;
(5) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (2) or (4), wherein ring B is

(6) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (5), wherein ring A is
(7) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (6), wherein X is -CON(R10) - (CH2)n- in which R10 and n each
has the same meaning as defined above;
(8) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (6), wherein X is -COO-(CH2)n- in which n has the same
meaning as defined above;
(9) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (7) or (8), wherein n is 0;
(10) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10), which is represented by the formula (1')

wherein
R2 and R2 are each independently hydrogen, C1-C6 alkyl,
C3-C7 cycloalkyl, C1-C6 alkoxy, halogen, halo C1-C6 alkyl, C1-C6
acyl, C2-C6 alkenyl or cyano;
X1 is -0- or -NR10- wherein R10 is hydrogen, C1-C6 alkyl
or C3-C7 cycloalkyl; and
R1, R3, R4, R5, R6, R7, R8, R9, ring C, 1 and m each has
the same meaning as defined above,
or a prodrug thereof, or a pharmaceutically acceptable salt of
either;
(11) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10), wherein the ring C is

, in which q is an integer of 0 to 3;
(12) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (11) , wherein X1 is -NR10- in which R10 has the same meaning
as defined above;
(13) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (11), wherein X1 is -O-;
(14) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10) to (13), wherein the group -(CH2)1- is located at
the h-position of the benzene ring in the formula (l);
(15) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10) to (13), wherein the group -(CH2)1- is located at
the i-position of the benzene ring in the formula (1');
(16) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10) to (15), wherein R8 and R9 are each independently
-CON(R18) (R19)- in which R18 and R19 each has the same meaning
as defined above;
(17) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (10) to (15), wherein R8 and R9 are each independently
-COO(R20)- in which R20 has the same meaning as defined above;
(18) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (12) to (17), wherein the ring C is C6-C14 aryl ;
(19) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (18), wherein C6-C14 aryl is phenyl;
(20) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (12) to (17), wherein the ring C is C3-C7 cycloalkyl;
(21) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (12) to (17), wherein the ring C is

(22) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-(4-[methyl-(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 9-(2,2,2-trifluoro-ethylcarbamoyl)-9h-
fluoren-9-ylmethyl ester,
2-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid 9-(2,2,2-trifluoro-
ethylcarbamoyl) -9h-fluoren-9-ylmethyl ester,
{4 -[(4'-trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2-(2,2,2-trifluoro-
ethylcarbamoyl) -ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 1-(2,2,2-trifluoro-ethylcarbamoyl)-
cyclopentylmethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisopropyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl )-ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester.
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 1-(2,2,2-trifluoro-ethylcarbamoyl)-
cyclohexylmethyl ester,
2-phenyl-2 -{2 -[4 -(2-trifluoromethyl-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4-(2-phenoxy-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2-butoxy-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-{2-[4-(2-trifluoromethyl-benzoyloxy)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4-(2-benzoyl-benzoyloxy)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2-benzoyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trif luoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethy1)-malonic acid
dicyclohexyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-phenyl-
ethyl ester,
{4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-ethyl
ester,
{4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-phenyl
ester,
2-butoxy-benzoic acid 4-[2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-phenyl
ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
[4-(2-phenoxy-benzoylamino)-phenyl]-acetic acid 2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethy1-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
(4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-propylcarbamoyl-ethyI
ester,
{4- [ ( 4 ' -trif luorome thy 1-biphenyl-2-car bony 1) -asalno] -
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(41-trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-phenyl
ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(41 -
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
[4-(2-butoxy-benzoylamino)-phenyl]-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2, 2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
2-(2-{4-[(9-oxo-9h-fluorene-1-carbonyl)-amino ] -
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2- (2-{4-[(9h-fluorene-1-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-1rifluoromethyl-biphenyl-2 -carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
[ 4- ( 2-phenoxy-iDenzoylamino) -phenyl] -acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
[4-(2-butoxy-benzoylamino)-phenyl]-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(31-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-(2-{4-[2-(4-fluoro-benzoyl)-benzoylamino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-2-chloro-
phenyl ester,
2-phenyl-2-{2-[4-(2-thiophen-3-yl-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-(2 -{4 -[(biphenyl- 3-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester.
2 -(2-{4 -[cyclohexyl-(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[4-(2-isopropyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2-benzyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
2-phenyl-2-{2-[4-(2-trifluoromethoxy-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4-(2-butoxycarbonyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl)- 2-
phenyl-ethyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
[4-(2-cyclohexyl-benzoylamino)-phenyl]-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-2-
phenyl-ethyl ester,
2-[2-(4-{[2-methyl-4-(4 -1rifluoromethyl-phenyl)-
thiazole- 5-carbonyl]-amino}-phenyl)-acetoxymethyl]-2 -
phenyl-malonic acid diethyl ester,
(4-{[2-methyl-4-(4 -trifluoromethyl-phenyl)-thiazole-
5-carbonyl]-amino}-phenyl)-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
(4-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-
carbonyl]-amino}-phenyl)-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
(3-methyl-4-{[2-(4-trifluoromethyl-phenyl)-pyridine-
3-carbonyl]-amino}-phenyl)-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2- (2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2 - (2 - {3-isopropyl-4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2 -(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-dimethylcarbamoyl- 4 -[(4'-trifluoromethy1-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl- 4 -[(4'-trifluoromethy1-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 4, 4-bis -
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethy1)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
{3-(isopropyl-methyl-carbamoyl)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetic
acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2 -(2 -{3 -(ethyl-methyl-carbamoyl)- 4 -[(4'-
trif luoromethy 1-biphenyl-2-carbonyl) -amino] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3 -(ethyl-methyl-carbamoyl)- 4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methyl-carbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)- 4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(41-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propyl-carbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propyl-carbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-ethylcarbamoyl--
2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrrolidine-1-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-1-carbonyl)- 4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2-(2,5-dioxo-
pyrrolidin-1-yl)-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2-ethylcarbamoyl-
benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2-
ethylcarbamoylmethyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-isopropylamino-2-
phenyl-ethyl ester hydrochloride,
[3-dimethylcarbam©yl-4-(2-trifluoromethyl-
benzoylamino) -phenyl] -acetic acid 2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-trifluoromethyl-
benzoylamino) -phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]- 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-fluoro-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-bromo-bipheny1-2 -carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethy1)-2-phenyl-malonic
acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-acetylamino-2-
phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-butyrylamino-2-
phenyl-ethyl ester,
[ 4- ( 2-benzoyl-'benzoylamino) -3-dimethylcarbamoyl-
phenyl]-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
2-{2-[4-(2-benzoyl-benzoylamino)- 3-dimethylcarbamoyl-
phenyl ]-acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid dimethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethy1-bipheny1-2-carbonyl)-amino]-phenyl}-acetoxy
methyl)-malonic acid diethyl ester,
2 -cyclohexyl-2-(2-{3-dimethylcarbamoyl- 4 - [ ( 4 ' -
trifluoromethy1-bipheny1-2-carbonyl)-amino]-phenyl}-acetoxy
methyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-bipheny1-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-bipheny1-2-carbonyl)-amino] - 3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
[3-dimethylcarbamoyl-4-(2-phenoxy-benzoylamino)-
phenyl]-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
2-{2-[3-dimethylcarbamoyl-4-(2-phenoxy-benzoylamino)-
phenyl]-acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
t r if luoromethyl -biphenyl-2-carbonyl) - amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-
methanesulfonylamino-2-phenyl-ethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2-phenyl-
propionic acid ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-(methyl-propionyl-
amino)-2-phenyl-ethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trif luorome thyl-biphenyl-2-carbonyl) -amino] -phenyl} -

acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl - 2 -
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester) ,
2-(2-{3-dimethylcarbamoyl- 4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(21-fluoro-4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trif luorome thyl-biphenyl- 2 -carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trif luorome thyl - biphenyl - 2 - carbonyl) - amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3 -dimethylcarbamoyl- 4 -[(3'-fluoro- 4'-
trif luorome thyl-biphenyl-2-carbonyl) -amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4-[ (4 ' -
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4 -[ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester.

2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-[(4
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(2-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)- amino]-phenyl}-acetoxymethyl)-2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4 -
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl- 2 -carbonyl) -amino ] -phenyl} -
acetoxy)-ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl- 2 -carbonyl) -amino] -phenyl} -

acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethy1-biphenyl-2 -carbonyl)-amino]-pheny1}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methoxy-4'-
trif luoromethyl - biphenyl - 2 - carbonyl) -amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2-{3 -dimethylcarbamoyl- 4 -[(3-methyl- 4 ' -
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}- 2 -phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-ethyl-4-trifluoromethyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) - 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'- isopropyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic

acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-isopropenyl-4-
trif luoromethyl-benzoylamino) -phenyl ] -acetoxymethyl} - 2 -
phenyl-malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-isopropyl-4-
trifluoromethyl-benzoylamino)-phenyl]-acetoxymethyl}-2 -
phenyl-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl-4 -[2 -(3-trifluoromethyl-
phenylamino)-benzoylamino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(4'-trifluoromethyl-
bipheny1-2 -carbonyloxy)-phenyl]-acetoxymethyl}- 2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[2-(3-trifluoromethyl-
phenoxy)-benzoylamino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-ethyl-2-phenyl-
butyl ester,
2-(2-{3-dimethylcarbamoyl-4-[2-(4-trifluoromethyl-
phenoxy)-benzoylamino]-phenyl}-acetoxymethyl)- 2-phenyl-
malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-diphenyl-ethyl
ester,
{3-dimethylcarbamoyl-4-[ ( 4'-trifluoromethyl-biphenyl-

2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3-hydroxy-2-
hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3-acetoxy-2-
acetoxymethyl-2-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2 -(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
isopropyl-malonic acid diethyl ester.

2-sec-butyl-2-(2-{3-dimethylcarbamoyl-4-[(41-
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
isobutyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
propyl-malonic acid diethyl ester,
2 -(2-{3-dimethylcarbamoyl- 4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-ethyl-
malonic acid diethyl ester,
2-butyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-allyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2,2-bis-
ethoxycarbonyl-propionic acid ethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -(1-
methyl-butyl)-malonic acid diethyl ester,
2-(2 - {3-ethoxy-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbony1)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-hydroxy-4 -[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl -

2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2 -

carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -phenyl-malonic
acid diethyl ester, "
2-{2-[3-methoxy-4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-phenyl-2-(2-{3 -piperidin-1-yl-4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(41-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,

2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-bipheny
1-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2 -carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{3- [(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic

acid diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-phenyl-
propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-ethylcarbamoyl-
4-phenyl-butyl ester,
{2-methyl-3- [ ( 4'-trif luorome thyl- biphenyl- 2-
carbonyl)-amino]-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2 -
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2 -{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[9-(2,2,2-trifluoro-ethylcarbamoyl)-9h-
fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-(9h-fluoren-9-yl)-ethyl ester,
n-biphenyl-2-yd-terephthalamic acid 2-[9-(2,2,2-
trifluoro-ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[(biphenyl-2-carbonyl)-amino]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-(2-biphenyl-2-yl-acetylamino)-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-naphthalen-l-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[2-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-diphenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
4 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-

benzole acid 3-phenyl-3-(2,2,2-trifluoro-ethylcarbamoyl)-
propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 2-[8-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3-(2,6-dichloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3-(2-chloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
2-{2- [4-(2 -benzoyl-benzoyloxy)-benzoyloxy]-ethyl}-2 -
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethy1-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid
4 -(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)- 2 -
chloro-phenyl ester.

4 ' -trifluoromethyl-biphenyl-2-carboxylic acid
4-(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-
dichloro-phenyl ester,
4-methyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-cyclohexanecarboxylic acid 2-[9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
cyclohexanecarboxylic acid 2-[9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
cyclohexanecarboxylic acid 3-phenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl)-propyl ester,
2-phenyl-2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-cyclohexanecarbonyloxymethyl}-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-cyclohexanecarbonyloxy}-ethyl)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-piperidin-1-yl}-acetoxymethy1)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-indol-1-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-benzoimidazol-1-yl}-acetoxymethyl)- 2 -

phenyl-malonic acid diethyl ester,
[2 -oxo-3-(4'-trifluoromethyl-biphenyl-2-carbonyl)-
2,3-dihydro-benzooxazol-6-yl]-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl ) -ainino ]-phenyl}-acetoxymethyl) - 2 -
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(41-trifluoromethyl-
biphenyl- 2 -carbonyl) -ainino] -phenyl}-propionyloxymethyl) -2-
phenyl-malonic acid diethyl ester,
4-{[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
methyl}-benzoic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
3-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid ethylcarbamoyl-phenyl-methyl
ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)- 2 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-benzoimidazol-1-yl}-acetoxymethyl)-maIonic
acid diethyl ester,
3- { [ ( 4 ' -trif luoromethyl-biphenyl-2 -carbonyl) -amino ].-

methyl}-benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid methyl ester,
2-(2-{3-benzylbxycarbonyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, "
2-{2-[2-oxo-3-(4'-trifluoromethyl-biphenyl-
2-carbonyl)-2,3-dihydro-benzooxazol-6-yl]-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-{2-[8-OXO-7-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-7-aza-bicyclo[4.2.0]octa-l(6),2,4-trien-3-yl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(3-dimethylcarbamoyl-4-{[1-(2-nitrol-4-trifluoro-
methy1-phenyl )-pyrrolidine-2-carbonyl]-amino}-phenyl)-
acetoxymethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester, .

2- (2-{3-me thoxycarbonylami.no-4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(41 -
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-pheriyl-malonic acid diethyl ester,
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-pheriyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(41-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(methoxy-methyl-carbamoyl)-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4- [(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxym
ethyl)-2-phenyl-malonic acid diethyl ester;
(23) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino] -

phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
2-phenyl-2-{2-[4-[(4'-trifluoromethyl-biphenyl-
2-carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2 -{3-methy!-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[methyl-(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, "
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis- ethylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-ylmethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid 9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-ylmethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisopropyl ester.

{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-t(4'-trifluoromethy1-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -p'henyl}-acetoxymethyl) -malonic acid
dicyclohexyl ester,
{4 -[(4'-trifluoromethyl-biphenyl-2-carbony1)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbony1)-amino]-phenyl}-acetoxymethyl-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl-2-phenyl-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2 -trifluoro-ethylcarbamoyl)-

ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2,2-trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-
phenyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-
ethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl-malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-phenyl
ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-

phenyl}- acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl}-amino]-
phenyl}- acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl) -2 -
chloro-phenyl ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-
biphenyl- 2 -carbonyl} -amino]-phenyl}-acetoxymethyl)- 2 -
phenyl-malonic acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,

2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
{4-t(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid "2,2-bis-(3-methyl-butylcarbamoyl-2-
phenyl-ethyl ester,
2-(2-{4 -[ethyl-(4'-1rifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-(ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethy1-biphenyl-2-
carbonyl}-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-
amino]-phenyl}-acetic acid 2,2-bis-(2-methoxy-
ethylcarbamoyl)-2-phenyl-ethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl}-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester.

{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl}-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-

ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4- [ (4 ' -trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 4,4'-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2
-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl )-amino]-phenyl}-acetoxymethyl)- 2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
{3-(isopropyl-methylcarbamoyl)-4-[(4'-trifluoro-
methyl-biphenyl-2 -carbonyl )-amino]-phenyl}-acetic acid 2,2-
bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2- (2-{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoro-

methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-l-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-ethyl ester,
{3-(dimethylcarbamoyl)- 4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-ethyl-
carbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrrolidine-1-carbony1)-4 -[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-1-carbony1)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl } -
acetoxymethyl)-malonic acid diethyl ester,

{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(2,5-
dioxo-pyrrolidin-1-yl)-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-
ethylcarbamoyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl}-amino]-phenyl}-acetic acid 2-
ethylcarbamoylmethyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-
isopropylamino-2-phenyl-ethyl ester hydrochloride,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-fluoro-biphenyl-
2-carbonyl}-amino]-phenyl}-acetoxymethyl)-2-phenyl- malonic
acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]- 3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
{3 -dimethylcarbamoyl- 4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-

acetylamino-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-
butyrylamino-2-phenyl-ethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid dimethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2 -carbonyl)-amino]- 3 -
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)- 2 -phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-
methanesulfonylamino-2-phenyl-ethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2-phenyl-
propionic acid ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(methyl-
propionyl-amino)-2-phenyl-ethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.

2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl- 2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl- 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-(3'-chloro- 4'-trifluoromethyl-
biphenyl-2 -carbonyl) - amino]-3 -dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
(5-nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-4
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl )-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -ami.no] -phenyl}-acetoxymethyl) -2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-araino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2- (3-chloro-phe-nyl) -2- ( 2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -2-
(2-methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2 -
(3-methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4 -
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-(5,4'-bis -trifluoromethyl-biphenyl-2-

Cc.rbonyl) - amino] -3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl}-malonic acid diethyl ester,
2-(2-{4-(6-chloro-4'-trifluoromethyl-biphenyl- 2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2-{3-dimethylcarbamoyl- 4-[(6-fluoro- 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-pheny1}-
acetoxymethyl)-2-pheriyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4'-bis-4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl- 4 -[(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester.

2-(2-{3-dimethylcarbamoyl-4 -[(4'-methyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-ethyl- 4 -
trifluoromethyl-benzoylamino)-phenyl]-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethy1)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyloxy)-phenyl]-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-ethyl-2-
phenyl-butyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-
diphenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyL-

cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-hydroxy-
2-hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-acetoxy-
2-acetoxymethyl-2-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-2-yl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl- 2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2, 2-bis -
ethylcarbamoyl- 2-phenyl-ethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid
3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4 -[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 2, 2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4 -[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbaraoyl-3-phenyl-propyl ester,

{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl- 2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl} -acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[ ( 4 ' -
trifluoromethyl- biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-

acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-
propyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis- propylcarbamoyl-
propyl ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2 -

carbonyl)-amino]-phenyl}-acetoxy-ethyl)-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-
phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 4,4-bis -
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester.

2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[9- (2,2,2-trifluoro-ethylcarbamoyl) -9h-
fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[9h-fluoren-9-yl]-ethyl ester,
n-biphenyl-2-yl-terephthalamic acid 2-[9-(2,2,2-
trifluoro-ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[(biphenyl-2-carbonyl)-amino]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-(2-biphenyl-2-yl-acetylamino)-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-naphthalen-l-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[2-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-diphenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester.

4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl)-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-phenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl)-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[8-(2,2,2-trifluoro-
ethylcarbamoyl)-naphthalen-1-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[(2,6-dichloro-phenyl)-3-
(2,2,2-trifluoro-ethylcarbamoyl)-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-(2-chloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-

bis -ethylcarbamoyl-3-phenyl-propoxycarbony)-2-chloro-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3, 3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3, 3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbony1)-2,6-dichloro-
phenyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl-acetoxymethy1)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino] -phenyl} -propionyloxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid ethylcarbamoyl-phenyl-
methyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbony1)-
amino]-benzoic acid ethyl ester,
5 -(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid methyl ester,
2-(2 -{3 -benzyloxycarbonyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropbxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4\-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl -2 -carbonyl )-amino]-phenyl}-3-acetoxymethyl) - 2-
phenyl-malonic acid diethyl ester.

2-(2-{3-methoxy-methylcarbamoyl) - 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-3-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-3-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester;
(24) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl)-2-phenyl-
ethyl ester,
2-phenyl-2-{2-[4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethy1)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[methyl-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-2-phenyl]-acetic acid 2,2-bis-
ethylcarbamoyl-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -

carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic acid
diisopropyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dicyclohexyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-
phenyl ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester.

2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2,2-trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-
phenyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-
ethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carbxylic acid
4 -(2,2-bis-ethylcarbamoyl)-2-phenyl-ethoxycarbonylmethyl)-

phenyl ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[ (4' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4 -[(4'-trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(2,2-bis-ethylcarbamoyl)-2 -phenyl-ethoxycarbonylmethyl)-
2-chloro-phenyl ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-biphenyl-2 -

carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
{4 -[(4'-1rifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-(3-methyl-
butylcarbamoyl)-2-phenyl-ethyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(3'4'-dichloro-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester.

{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-2
phenyl-ethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl )-amino]-phenyl}-acetoxymethyl)- 2-

phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propy1 ester,
2-(2-{3-diethyicarbamoyl-4-[(4'-trifluoromethyl-
biphfcnyl-2-carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl- 4-[(4'-1rifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4- [ ( 4 ' -trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethy1-biphen
yl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-(isopropyl-methylcarbamoyl)-4-[(4'-trifluoromethyl
-biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbony1)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-ethylcarbamoyl-2-phenyl-ethyl ester.

2-phenyl-2-(2-{3-pyrrolidin-1-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-carbonyl)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(2,5-
dioxo-pyrrolidin-1-ylj-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-ethylcarbamoyl-benzyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-ethylcarbamoylmethyl-benzyl ester,
{3 -dimethylcarbamoyl-4-[(4'-1rifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-isopropylamino-2-phenyl-ethyl ester hydrochloride,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-fluoro-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)- 2-phenyl-malonic

acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-acethylamino-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-butyrylamino-2-phenyl-ethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethy1)-
2-phenyl-malonic acid dimethyl ester,
2 - cyclopen tyl-2 - ( 2 - { 3 - dime thylcarbamoyl- 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4 ' -
trifluoromethy1-biphenyl- 2-carbony1)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
trifluromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl- 4 -[(5-methyl- 4'-

trifluromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-methanesulfonylamino-2-phenyl-ethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2-phenyl-
propionic acid ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(methyl-
propionyl-amino)-2-phenyl-ethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluromethyl-
-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl- 4 -[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.

2-(2-{5-dimethylcarbamoyl-2-fluoro-4 -[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4 ' -
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)- malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoy1-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-

acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phfenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2- (2-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-pherryl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl- 4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbony1)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-(5,4'-bis-trifluoromethyl-biphenyl- 2 -
carbony1)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.

2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino) - 3 -
dimethylcarbamoyl-phenyl]-acetoxymethyl}-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4 -[(2-ethyl- 4 -
trifluoromethyl-benzoylamino)-phenyl]-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl) -amino] -phehyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyloxy)-phenyl]-acetoxymethyl}- 2 -
phenyl-malonic acid diethyl ester,
{3 -dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-ethyl-
2-phenyl-butyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic = acid 2,2-

diphenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-hydroxy-
2-hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
3-acetoxymethyl-2-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl]-2-
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl]-2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl]-2 -(3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2 -

carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamtfyl-2-phenyl-ethyl ester
{3y/methoxy-4- [ (4 ' -trifluoromethyl-biphenyl-2-
carbbffyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, -
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)- amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester.

{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4f-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy) -phenyl] -acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[ ( 4'-trifluoromethyl-biphenyl-
2- carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-

acetoxymethyl)- malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-1-yl- 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethy1-biphenyl- 2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-
propyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-
propyl ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2-

carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2 -methyl-5-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-
phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4f-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester.

2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-t2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[(bipftenyl-2-carbonyl)-amino]-ethyl ester,
4- [(4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-(2-biphenyl-2-yl-acetylamino)-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2 -carbonyl)-amino]-
benzoic acid 3-naphthalen-l-yl-3-(2,2,2-
trifluoroethylcarbamoyl)-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[2-(2,2,2-trifluoro-
ethylcarbamoyl) -naphthalen-1-yl]-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-diphenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
4 - [(4'-trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-
benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-phenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl )-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-

benzole acid 2-[8-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3-(2,6-dichloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3-(2-chloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-malonic acid diethyl
ester,
2-(2-{3-methyl-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2 -{2-chloro-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2-chloro-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl
ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-dichloro-p

henyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-propionyloxymethyl)-
2-phenyl-malonic acid diethyl ester,
3-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid ethylcarbamoyl-phenyl-
methyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl- 2-phenyl-ethoxycarbony1-
methyl)-2-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid ethyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid methyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2-phenyl-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)- malonic acid
diethyl ester,
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2 -{3-dimethylaminomethyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2 -(2 -{3 -(methoxy-methylcarbamoyl)- 4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2- (2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl )-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, and

2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester;
(25) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-ethyl-4-[(4f-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcaramoyl-2-phenyl-
ethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-

(2,2,2-trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-
phenyl ester,
{4- [ (biphenyl-2-carbonyl) -ami.no] -phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-phenyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis- butylcarbamoyl-2-phenyl-ethyl-
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl ethyl ester,
4'-trif luoromethyl-biphenyl-2-carboxylic acid 4-(2., 2-

bis-ethylcarbamoyl- 2 -pheny1-ethoxycarbonylmethyl) - 2 -chloro-
phenyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl)-2-
phenyl ethyl ester,
{4-[(4'-chloro-bipheny1-2-carbony1)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl ethyl ester,
{4-t(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl)-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl)-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-
2-phenyl-ethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-phenyl-ethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2, 2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylearbamoyl-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl} -acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl} -acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-pheiiyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(isopropyl-methylcarbamoyl)- 4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetic
acid 2,2-bis- ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester.

{3-(piperidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-

ethylcarbamoyl-3-phenyl-propyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{3-t(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-
propyl ester,
{3-;[ (4 ' -trifluoromethy 1-biphenyl-2-carbonyl) -amino] -

phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-phenyl-
propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)- 2 -chloro-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-dichloro-
phenyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbony1-
methyl)- 2-[(4'-trifluoromethyl-biphenyl-2-carbony1)-

amino]-benzole acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbony1-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzole acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzole acid ethyl ester, and
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzole acid methyl ester;
(26) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[methyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisopropyl ester.

2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dicyclohexyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2- carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-

acetoxymethyl)- malonic acid diethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-(2-{4-[isopropyl-(4'-1rifluoromethy1-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,'
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropyl-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester.

2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoro-
me thyl- biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-(pyrroldine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrroldine-1-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-1-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-

acetoxymethyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]- 3 -
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-
3-dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-
3-dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-

trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.

2-(2-{3-chloro-5-dimethylcarbamoyl- 4 - [ ( 4 ' -
trifluoromethyl-bipheny1-2-carbony1)-amino]-pheny1}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-pheny1}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2 -(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl- 4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbony1)-amino]-phenyl}-acetoxymethyl) -2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-
[(4'-trifluoromethyl-biphenyl-2-carbony1)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3-bromo- 5-dimethylcarbamoyl- 2 -fluoro- 4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbony1)-amino]-phenyl}-acetoxymethyl)-2-m-

tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl- 4 -
[(4'-trifluoromethyI-biphenyl-2-carbonyl)-amino]-phenyl}
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}
acetoxymethyl)-malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl- 4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(2-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trif luoromethyl--
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- 3-dimethylcarbamoyl-phenyl)-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2 -

carbony1)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]-2-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethy1-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-pheriyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl- 2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}-2-phenyl)-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(4'-methyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester.

2-{2-[3-dimethylcarbamoyl-4-[(2-ethyl-4-trifluoro-
methyl-benzoylamino)-phenyl]-acetoxymethyl}-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
-biphenyl-2-carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-2-yl- malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-3-yl- malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)-
2-phenyl- malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2 -(5-

methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phehyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isoprbpoxy-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-

biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-1rifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester, "
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
2- [ 2 - (.2 - { 4 -methyl- 3 - [ ( 4 ' - trif luoromethyl-biphenyl - 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester.

2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino ] -bertzoyloxy} -ethyl ] -malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{2-chloro-4 -[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl -2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl -2 -carbonyl )-amino]-phenyl}-propionyloxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-benzyloxycarbony-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
phenyl-malonic acid diethyl ester.

2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4'-trifluoro-
methyl -biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2 -(2 -{3 -formyl- 4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(methoxy-methylcarbamoyl)- 4 -[(4'-trifluoro-
methyl-biphenyl-2-carbonyl )-amino]-phenyl}-acetoxymethyl)-

2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl) - 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbony1)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester;
(27) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is Selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2 -carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-
phenyl-ethyl ester,
{4 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-
phenyl-ethyl ester.

{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethyl-
carbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl-
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propyl- carbamoyl-
propyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl)- 2 -
phenyl-ethyl ester,

{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-
2-phenyl-ethyl ester.
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethyl-
carbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethyl-
carbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,

{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl) -amino] -phenyl} -ace tic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyiy-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(isopropyl-methylcarbamoyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester.

{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2 -phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid ethyl ester, and
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid methyl ester;
(28) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the

above (1), which is selected from the group consisting of
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[methyl-(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisopropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dicyclohexyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethy1-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-cyclohexyl-2- ( 2-{ 4- [ ( 4 ' - trif luorome thy 1-biphenyl--
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-pyridin-2-yl- 2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2-phenyl-2-(2-{3-trifluoromethyl-4 -[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-ethyl-4-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropyl-4-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isobutyl-4 -(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) - 2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -2
-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrrolidine-l-carbonyl)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-1-carbonyl) - 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-fluoro-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]}-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid dimethyl ester.
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl- 4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4f-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-trifluoro-
methyl- biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2
-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-trifluoro-
methyl -biphenyl -2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2
-phenyl-malonic acid diethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid 2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4- [ (4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[ (4 ' -
trifluoromethy1-biphenyl- 2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-(5 -
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2 -(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) —2 -
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4 '
trifluoromethy1-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) —2 - o -
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethyl) —2 -m -
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethyl) —2 - p -
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—malonic acid diethyl ester,
2 -(3 -chloro-phenyl)-2-(2-{3-dimethylcarbamoyl- 4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl} -
acetoxymethyl)—malonic acid diethyl ester.
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(2
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4f-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- 3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl- 4 -[(5-methyl- 4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-(6-methoxy-4'-trifluoro-
methyl -biphenyl- 2 -carbonyl ) -amino] -phenyl} -acetoxymethyl ) —
2-phenyl-malonic acid diethyl ester,
2 - (2-{3-dimethylcarbamoyl-4-(3-methyl-4'-1rifluoro-
methyl-biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) —
2-phenyl-malonic acid diethyl ester,
2-{2-{4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl] -acetoxymethyl}—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl)— 2-phenyl-malonic
acid diethyl ester,
2 - {2-[3-dimethylcarbamoyl- 4 -(2 -ethyl-4 -trifluoro-
methyl-benzoylamino) -phenyl] -acetoxymethyl}—2-phenyl-
malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl)— 2-phenyl-malonic
acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl - 2 - carbonyl) - amino ] - phenyl} - acetoxymethyl) —2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl- biphenyl-
2 -carbonyl) -amino] -phenyl} -acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2 -
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2 -
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)—
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(3-
methyl-thiophen-2-yi)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2 -
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2 -(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester.
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethy1) -
malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -
malonic acid diethyl ester,
2-(2 -{3-dimethylamino- 4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethy1)—2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethy1)—2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethy1)—2 -
phenyl-malonic acid diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-propionyloxymethyl)-
-2-phenyl-malonic acid diethyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{3-formyl- [ ( 4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(methoxy-methylcarbamoyl)- 4 -[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2- phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester;
(29) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2,2-trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2, 2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-phenyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2 -phenyl-ethoxycarbonylmethyl)- 2 -
chloro-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl- 3 -phenyl-propoxycarbonylmethy1)- 2 -
chloro-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl ester,
and
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-dichloro-p
henyl ester;
(30) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-{2-[3-dimethylcarbamoyl-4-(4'-trifluoromethyl-
biphenyl-2-carbonyloxy)-phenyl]-acetoxymethyl}- 2-phenyl-
malonic acid diethyl ester,
2-{2-[3-methoxy-4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl malonic acid
diethyl ester, and
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[ 2-( 2 , 2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-propyl ester;
(31) The ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to the
above (1), which is selected from the group consisting of
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
isopropyl-malonic acid diethyl ester,
2 -sec-butyl-2-(2-{3-dimethylcarbamoyl- 4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
isobutyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
propyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-ethyl-
malonic acid diethyl ester,
2-butyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- malonic acid diethyl ester,
2-allyl-2-(2-{3-dimethylcarbamoyl-4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2,2-bis-
ethoxycarbonyl-propionic acid ethyl ester, and
2 -(2-{3-dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(1-
methyl-butyl)-malonic acid diethyl ester;
(32) A pharmaceutical composition, which comprises the ester
compound or a prodrug thereof, or a pharmaceutically acceptable
salt of either according to any of the above (1) to (31) and
a pharmaceutically acceptable carrier;
(33) An MTP (microsomal triglyceride transfer protein)
inhibitor, which comprises the ester compound or a prodrug
thereof, or a pharmaceutically acceptable salt of either
according to any of the above (1) to (31) as an active ingredient ;
( 34 ) An agent for the treatment or prophylaxis of hyperlipidemia,
which comprises the ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to any of
the above (1) to (31) as an active ingredient;
(35) An agent for the treatment or prophylaxis of
arteriosclerosis, which comprises the ester compound or a
prodrug thereof, or a pharmaceutically acceptable salt of
either according to any of the above (1) to (31) as an active
ingredient;
(36) An agent for the treatment or prophylaxis of coronary
artery diseases, which comprises the ester compound or a prodrug
thereof, or a pharmaceutically acceptable salt of either
according to any of the above (1) to ( 31) as an active ingredient ;
(37) An agent for the treatment or prophylaxis of obesity, which
comprises the ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to any of
the above (1) to (31) as an active ingredient;
(38) An agent for the treatment or prophylaxis of diabetes,
which comprises the ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to any of
the above (1) to (31) as an active ingredient;
(39) An agent for the treatment or prophylaxis of hypertension,
which comprises the ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to any of
the above (1) to (31) as an active ingredient;
(40) An agent for the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension, which comprises MTP inhibitor selectively
inhibiting MTP (microsomal triglyceride transfer protein) in
the small intestine and a pharmaceutically acceptable carrier;
(41) The agent for the treatment or prophylaxis according to
the above (40) , wherein the MTP inhibitor does not substantially
inhibit MTP in the liver but substantially inhibits only MTP
in the small intestine;
(42) The agent for the treatment or prophylaxis according to
the above (41), wherein after the administered MTP inhibitor
inhibits MTP in the small intestine, it is metabolized in the
small intestine, blood and liver to the amount at which the
remaining MTP inhibitor in the liver does not substantially
inhibit the MTP in the liver;
(43) The agent for the treatment or prophylaxis according to
the above (42) , wherein the remaining MTP inhibitor in the liver
is metabolized to the state where TG-releasing activity of the
liver is kept at the level of about 80% or more of the normal
level;
(44) The agent for the treatment or prophylaxis according to
the above (40) to (43), wherein the MTP inhibitor is a compound
having at least one ester bond;
(45) The agent for the treatment or prophylaxis according to
the above (44) , wherein after the compound having at least one
ester bond exerts MTP inhibitory activity, the ester moiety of
the compound is metabolized in blood to become an inactive
substance;
(46) The agent for the treatment or prophylaxis according to
the above (40) to (45), wherein the MTP inhibitor is the ester
compound or a prodrug thereof, or a pharmaceutically acceptable
salt of either mentioned in any of the above (1) to (31);
( 47 ) A method for the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension, which comprises administering a compound
selectively inhibiting MTP (microsomal triglyceride transfer
protein) in the small intestine;
(48) The method according to the above (47), wherein after the
compound inhibits MTP in the small intestine, it is metabolized
in the small intestine, blood and liver to the amount at which
remaining said compound in the liver does not substantially
inhibit MTP in the liver;
(49) The method according to the above (47), wherein the
remaining compound in the liver is metabolized to the state
where TG-releasing activity of the liver is kept at the level
of about 80% or more of the normal level;
(50) The method according to the above (47) to (49), wherein
the compound has at least one ester bond;
(51) The method according to the above (50), wherein after the
compound having at least ester bond exerts MTP inhibitory
activity, the ester moiety of the compound is metabolized in
blood to become an inactive substance;
(52) The method according to the above (47) to (52), wherein
the compound is the ester compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either mentioned in any of
the above (1) to (31) ;
(53) The agent for the treatment or prophylaxis according to
the above (40) to (46), wherein the agent is an agent for the
treatment or prophylaxis of hyperlipidemia which is used in
combination with other antihyperlipidemic drug(s);
(54) The agent for the treatment or prophylaxis according to
the above (53), wherein other antihyperlipidemic drug is a
statin-type drug;
(55) The agent for the treatment or prophylaxis according to
the. above (54), wherein the statin-type drug is one or more
drug(s) selected from the group consisting of lovastatin,
simvastatin, pravastatin, fluvastatin, atorvastatin and
cerivastatin;
(56) The agent for the treatment or prophylaxis according to
the above (40) to (46), wherein the agent is an agent for the
treatment or prophylaxis of obesity which is used in combination
with other anti-obesity drug(s);
(57) The agent for the treatment or prophylaxis according to
the above (56), wherein other anti-obesity drug is mazindol
or/and orlistat; ^
(58) The agent for the treatment or prophylaxis according to
the above (40) to (46), wherein the agent is an agent for the
treatment or prophylaxis of diabetes which is used in
combination with other anti-diabetic drug(s);
(59) The agent for the treatment or prophylaxis according to
the above (58) , wherein other anti-diabetic drug is one or more
drug(s) selected from the group consisting of insulin
preparations, sulfonylurea drugs, insulin secretagogues,
sulfonamide drugs, biguanide drugs, a-glucosidase inhibitors
and insulin resistance-improving drugs;
(60) The agent for the treatment or prophylaxis according to
the above (59) , wherein other anti-diabetic drug is one or more
drug(s) selected from the group consisting of insulin,
glibenclamide, tolbutamide, glyclopyramide, acetohexamide,
glimepiride, tolazamide, gliclazide, nateglinide, glybuzole.

metformin hydrochloride, buformin hydrochloride, boglibose,
acarbose and pioglitazone hydrochloride;
(61) The agent for the treatment or prophylaxis according to
the above (40) to (46), wherein the agent is an agent for the
treatment or prophylaxis of hypertension which is used in
combination with other anti-hypertension drug(s);
(62) The agent for the treatment or prophylaxis according to
the above (61), wherein other anti-hypertension drug is one or
more drug(s) selecfed from the group consisting of loop
diuretics, angiotensin converting enzyme inhibitors,
angiotensin II receptor antagonists, calcium antagonists,
(3-blockers, a,|3-blockers and a-blockers;
(63) The agent for the treatment or prophylaxis according to
the above (62), wherein other anti-hypertension drug is one or
more drug(s) selected from the group consisting of furosemide
delayed release, captopril, captopril delayed release,
enalapril maleate, alacepril, delapril hydrochloride,
silazapril, lisinopril, benazepril hydrochloride, imidapril
hydrochloride, temocapril hydrochloride, quinapril
hydrochloride, trandolapril, perindopril erbumine, losartan
potassium, candesartan cilexetil, nicardipine hydrochloride,
nicardipine hydrochloride delayed release, nilvadipine,
nifedipine, nifedipine delayed release, benidipine
hydrochloride, diltiazem hydrochloride, diltiazem
hydrochloride delayed release, nisoldipine, nitrendipine,
manidipine hydrochloride, barnidipine hydrochloride,

efonidipine hydrochloride, amlodipine besylate, felodipine,
cilnidipine, aranidipine, propranolol hydrochloride,
propranolol hydrochloride delayed release, pindolol, pindolol
delayed release, indenolol hydrochloride, carteolol
hydrochloride, carteolol hydrochloride delayed release,
bunitrolol hydrochloride, bunitrolol hydrochloride delayed
release, atenolol, asebutolol hydrochloride, metoprolol
tartrate, metoprolol tartrate delayed release, nipradilol,
penbutolol sulfate, tilisolol hydrochloride, carvedilol,
bisoprolol fumarate, betaxolol hydrochloride, celiprolol
hydrochloride, bopindblol malonate, bevantolol hydrochloride,
labetalol hydrochloride, arotinolol hydrochloride, amosulalol
hydrochloride, prazosin hydrochloride, terazosin
hydrochloride, doxazosin mesylate, bunazocin hydrochloride,
bunazocin hydrochloride delayed release, urapidil and
phentolamine mesylate;
(64) Use of the agent for the treatment or prophylaxis according
to the above (34) to (46) and other antihyperlipidemic drug(s)
for the treatment or prophylaxis of hyperlipidernia;
(65) The use according to the above (64), wherein other
antihyperlipidemic drug is a statin-type drug;
(66) The use according to the above (64), wherein the
statin-type drug is one or more drug(s) selected from the group
consisting of lovastatin, simvastatin, pravastatin,
fluvastatin, atorvastatin and cerivastatin;
(67) Use of the agent for the treatment or prophylaxis according
to the above (34) to (46) and other anti-obesity drug(s) for
the treatment or prophylaxis of obesity;
(68) The use according to the above (67), wherein other
anti-obesity drug is mazindol or/and orlistat;
(69) Use of the agent for the treatment or prophylaxis according
to the above (34) to (46) and other anti-diabetic drug(s) for
the treatment or prophylaxis of diabetes;
(70) The use according to the above (69), wherein other
anti-diabetic drugs are one or more drug(s) selected from the
group consisting of insulin preparations, sulfonylurea drugs,
insulin secretagogues, sulfonamide drugs, biguanide drugs,
a-glucosidase inhibitors and insulin resistance improving
drugs;
(71) The use according to the above (70), wherein other
anti-diabetic drug is one or more drug(s) selected from the
group consisting of insulin, glibenclamide, tolbutamide,
glyclopyramide, acetohexamide, glimepiride, tolazamide,
gliclazide, nateglini.de, glybuzole, metf ormin hydrochloride,
buformin hydrochloride, boglibose, acarbose and pioglitazone
hydrochloride;
(72) Use of the agent for the treatment or prophylaxis according
to the above (34) to (46) and other anti-hypertension drug(s)
for the treatment or prophylaxis of hypertension;
(73) The use according to the above (72), wherein other
anti-hypertension drug is one or more drug(s) selected from the
group consisting of loop diuretics, angiotension converting
enzyme inhibitors, angiotension II receptor antagonists,
calcium antagonists, beta-blockers, alpha/beta blockers and
alpha blockers;
(74) The use according to the above (73), wherein other
anti-hypertension drug is one or more drug(s) selected from the
group consisting of furosemide delayed release, captopril,
captopril delayed release, enalapril maleate, alacepril,
delapril hydrochloride, silazapril, lisinopril, benazepril
hydrochloride, imidapril hydrochloride, temocapril
hydrochloride, quinapril hydrochloride, trandolapril,
perindopril erbumine, losartan potassium, candesartan
cilexetil, nicardipine hydrochloride, nicardipine
hydrochloride delayed release, nilvadipine, nifedipine,
nifedipine delayed release, benidipine hydrochloride,
diltiazem hydrochloride, diltiazem hydrochloride delayed
release, nisoldipine, nitrendipine, manidipine hydrochloride,
barnidipine hydrochloride, efonidipine hydrochloride,
amlodipine besylate, felodipine, cilnidipine, aranidipine,
propranolol hydrochloride, propranolol hydrochloride delayed
release, pindolol, pindolol delayed releases, indenolol
hydrochloride, carteolol hydrochloride, carteolol
hydrochloride delayed release, bunitrolol hydrochloride,
bunitrolol hydrochloride delayed release, atenolol,
asebutolol hydrochloride, metoprolol tartrate, metoprolol
tartrate delayed release, nipradilol, penbutolol sulfate,
tilisolol hydrochloride, carvedilol, bisoprolol fumarate,
betaxolol hydrochloride, celiprolol hydrochloride, bopindolol
malonate, bevantolol hydrochloride, labetalol hydrochloride,
arotinolol hydrochloride, amosulalol hydrochloride, prazosin
hydrochloride, terazosin hydrochloride, doxazosin mesylate,
bunazocin hydrochloride, bunazocin hydrochloride delayed
release, urapidil and phentolamine mesylate;
(75) A pharmaceutical composition comprising an effective
amount of the ester- compound or a prodrug thereof, or a
pharmaceutically acceptable salt of either according to any of
the above (1) to (31), a pharmaceutically acceptable,
appropriate amount of ethanol and propylene glycol fatty acid
ester;
(76) The pharmaceutical composition according to the above (75) ,
which comprises 25 to 35% by weight of ethanol and 65 to 75%
by weight of propylene glycol fatty acid ester;
(77) A capsule formulation comprising the pharmaceutical
composition according to the above (75) or (76);
(78) The capsule formulation according to the above (77),
wherein the capsule formulation is a hard capsule or soft
capsule;
(79) A biphenyl compound represented by the formula (100)
wherein
R1" is hydrogen, C1-C6 alkyl, halogen, halo C1-C6 alkyl or
C1-C6 alkoxy;
R2" is hydrogen, C1-C6 alkyl, halogen, halo C1-C6 alkyl
or C2-C6 alkenyl;
R3" is -CON(Rlla)(R12a) wherein Rlla and R12a are each
independently hydrogen, C1-C6 alkyl, optionally substituted
C6-C14aryl, optionally substituted C7-C16 aralkyl, C1-C6 alkoxy,
or Rlla and R12a may be taken together with the nitrogen to which
they are attached to form

(in which p is an integer of 0 to 2);
R4 is hydrogen, halogen, C1-C6 alkyl or halo C1-C6 alkyl;
R50 is hydrogen, C1-C6 alkyl, optionally substituted C6-C14
aryl or optionally substituted C7-C16 aralkyl; and
la is an integer of 1 to 3,
or a prodrug thereof, or a pharmaceutically acceptable salt of
either; and
(80) The biphenyl compound according to the above (79),
wherein
R1 is hydrogen,
R2 " is halo C1-C6 alkyl,
R3" is -CON(Rllb)(R12b) wherein Rllb and R12b are each
independently hydrogen or C1-C6 alkyl, or Rllb and R12b may be taken
together with the nitrogen to which they are attached to form

(in which p is an integer of 0 to 2),
R4 is hydrogeii, and
R50 is hydrogen or C1-C6 alkyl,
or a prodrug thereof, or a pharmaceutically acceptable salt of
either.
The definitions of each substituent used in the present
invention are as follows.
"C1-C6 alkyl" refers to a straight- or branched-chain
alkyl group having 1 to 6 carbon atom(s), and its example
includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl,
tert-pentyl or hexyl, etc., preferably a straight- or
branched-chain alkyl group having 1 to 4 carbon atom(s), more
preferably methyl, ethyl or isopropyl. Preferable examples
for R1, R2, R2 and R2 include methyl, ethyl or isopropyl;
preferable examples for R3 and R4 include methyl, ethyl, propyl,
isopropyl, butyl or isobutyl; a preferable example for R5, R6
and R7 includes methyl; preferable examples for R8 and R9 include
methyl or ethyl; preferable examples for R10 include methyl,

ethyl or isopropyl; preferable examples for R11 and R12 include
methyl, ethyl, propyl or isopropyl; preferable examples for R13
and R14 include methyl or ethyl; a preferable example for R15
includes isopropyl; preferable examples for R16 and R17 include
methyl or ethyl; preferable examples for R18 and R19 include
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,
tert-butyl, pentyl or isopentyl, more preferably ethyl;
preferable examples for R20 include methyl, ethyl, propyl,
isopropyl or isobutyl, more preferably ethyl; a preferable
example for R21 and R22 includes methyl; and preferable examples
for D include ethyl, propyl, isopropyl, butyl, isobutyl,
sec-butyl, sec-pentyl, etc.
Examples of the substituent for "optionally substituted
C1-C6alkyl" include halogen, carboxyl, hydroxy, amino, nitro,
cyano, C1-C6 alkoxy, C7-C16 aralkyloxy, C2-C7 alkoxycarbonyl,
C6-C14 aryl, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6
alkylsulfonyl, C1-C6 alkylamino, acylamino and the like, among
which hydroxy is preferable. The number of the substituents
is 1 to 5, preferably 1 to 3.
"C3-C7 cycloalkyl" refers to a cycloalkyl having 3 to 7
carbon atoms, specifically cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl, 1-methylcyclohexyl or cycloheptyl.
Preferable examples thereof include a cycloalkyl having 3 to
6 carbon atoms, specifically cyclopropyl, cyclobutyl,
cyclopentyl or cyclohexyl. More preferable examples thereof
include cyclopropyl or cyclohexyl. A preferable example for
R1 and R2 includes cyclohexyl; a preferable example fox- R10
includes cyclohexyl; a preferable example for R18 and R19
includes cyclohexyl; a preferable example for R20 includes
cyclohexyl; and preferable examples for ring C include
cyclopentyl or cyclohexyl. It is also preferable that R8 and
R9 are taken together to form cyclopentyl or cyclohexyl.
"C1-C6 alkoxy" refers to a straight- or branched-chain
alkoxy group having 1 to 6 carbon atom(s), and its example
includes methoxy, ethoxy, propoxy, isopropoxy, butoxy,
tert-butoxy, pentyloxy, tert-pentyloxy or hexyloxy, etc.,
preferably an alkoxy having 1 to 4 carbon atom(s), such as
methoxy, ethoxy, isopropoxy, butoxy or tert-butoxy, and more
preferably methoxy or ethoxy. Preferable examples for R1, R2,
R2 and R2 include methoxy, isopropoxy or butoxy; preferable
examples for R3 and R4 include methoxy, ethoxy, propoxy or
isopropoxy; preferable examples for R5, R6 and R7 include methoxy
or ethoxy; a preferable example for R11 and R12 includes methoxy;
and preferable examples for R15 include methoxy, ethoxy, propoxy
or isopropoxy.
"Halogen" refers to chlorine, bromine, fluorine or the
like. Preferable examples for R1 include fluorine or chlorine;
preferable examples for R2 and R2 include fluorine, chlorine
or bromine; preferable examples for R3 and R4 include chlorine
or bromine; and preferable examples for R5, R6 and R7 include
fluorine or chlorine.
"Halo C1-C6 alkyl" refers to said C1-C6 alkyl substituted
with said halogen, and its example includes chloromethyl,
bromomethyl, fluoromethyl, trifluoromethyl, trichloromethyl,
tribromomethyl, trichloroethyl, pentafluoropropyl or
chlorobutyl, etc., preferably chloromethyl, bromomethyl,
fluoromethyl, trifluoromethyl, trifluoroethyl or
trichloromethyl, and more preferably trifluoromethyl. A

preferable example for R1, R2, R2' and R2" includes
trifluoromethyl; a preferable example for R3 and R4 includes
trifluoromethyl; a preferable example for R5, R6 and R7 includes
trifluoromethyl; preferable examples for R16 and R17 include
trifluoromethyl or trifluoroethyl; and preferable examples for
R18 and R19 include trifluoromethyl or trifluoroethyl.
"Halo C1-C6 alkyloxy" refers to, for example,
chloromethyloxy, bromomethyloxy, fluoromethyloxy,
trifluoromethyloxy, trichloromethyloxy, tribromomethyloxy,
trichloroethyloxy, pentafluoropropyloxy or chlorobutyloxy,
etc., preferably chloromethyloxy, bromomethyloxy,
fluoromethyloxy, trifluoromethyloxy or trichloromethyloxy,
and more preferably trifluoromethyloxy. A preferable example
for R1, R2, R2' and R2" includes trif luoromethyloxy.
"C2-C12 alkoxyalkyl" refers to an alkoxyalkyl of which
alkoxy moiety has the same meaning as said alkoxy and alkyl
moiety has the same meaning as said alkyl, and its example
includes methoxymethyl, ethoxymethyl, propoxymethyl,
butoxymethyl, pentyloxymethyl, hexyloxymethyl, ethoxyethyl or
methoxyethyl, etc. A preferable example for R18 and R19 includes
methoxyethyl.
"C2-C7 alkylcarbonyl" refers to acetyl, propionyl,
butyryl or pivaloyl, etc., and a preferable example for R21 and
R22 includes acetyl.
"C1-C7 alkylsulfonyl" refers to methanesulfonyl,
ethanesulfonyl, propylsulfonyl, butylsulfonyl,
pentylsulf onyl or hexylsulf onyl, etc. , and a preferable example
for R21 and R22 includes methylsulf onyl.
"C2-C7 alkoxycarbonyl" refers to an alkoxycarbonyl of

which alkyl moiety has 1 to 6 carbon atom(s) such as
methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,
tert-butoxycarbonyl, pentyloxycarbonyl,
tert-pentyloxycarbonyl or hexyloxycarbonyl, etc. Preferable
examples thereof include methoxycarbonyl, ethoxycarbonyl,
propoxycarbonyl or butoxycarbonyl. A preferable example for
R2 includes butoxycarbonyl; a preferable example for R5, R6 and
R7 includes methoxycarbonyl; a preferable example for R13 and
R14 includes methoxycarbonyl; and a preferable example for D
includes ethoxycarbonyl.
"C1-C6 acyl" refers to formyl having one carbon atom, or
an alkanoyl having 2 to 6 carbon atoms such as acetyl, propionyl,
butyryl or pivaloyl, etc., and its preferable examples include
formyl, acetyl or pivaloyl. A preferable example for R2 and
R2 includes acetyl; a preferable example for R3 includes formyl;
a preferable example for R5, R6 and R7 includes acetyl; a
preferable example for R13 and R14 includes acetyl; and a
preferable example for R21 and R22 includes acetyl.
"Alkanediyl" has preferably 1 to 6 carbon atom(s), and
its example includes methylene, ethane-1,2-diyl,
ethane-1,1-diyl, propane-1,3-diyl, butane-1,4-diyl,
pentane-1,5-diyl, hexane-1,6-diyl,
1,1-dimethylethane-l,2-diyl, 1,1-diethylethane-l,2-diyl,
2,2-dimethylethane-l,2-diyl, 2,2-diethylethane-1,2-diyl,
1,1-dimethylpropane-l,3-diyl, 1,1-diethylpropane-l,3-diyl,
2,2-dimethylpropane-l,3-diyl, 2,2-diethylpropane-l,3-dlyl,
3,3-dimethylpropane-1,3-diyl or 3,3-diethylpropane-l,3-diyl,
etc. Preferable examples for Alk1 and Alk2 include methylene.
ethane-1,2-diyl, ethane-1,1-diyl, propane-1,3-diyl, etc.
"Alkenediyl" has preferably 2 to 6 carbon atom(s), and
its example includes ethylene-1,2-diyl, 1-propene-l,3-diyl,
2-propene-1,3-diyl, 1-butene-l,4-diyl, 2-butene-l,4-diyl,
3-butene-l,4-diyl or 1,3-butadiene-l,4-diyl, etc. Preferable
examples for Alk1 and Alk2 include ethylene-1,2-diyl,
1-propene-l,3-diyl, 2-propene-1,3-diyl, etc.
"C6-C14aryl" refers tophenyl, naphthyl or biphenyl, etc. ,
preferably phenyl.
In the "optionally substituted C6-C14 aryl", the
substituent(s) is/are not particularly limited, and may be the
same or different each other and is/are arbitrarily positioned.
The number of substituents is not particularly limited so long
as they are chemically acceptable, while the number is
preferably around 1 to 3. Specifically, examples of the
substituent include C1-C6 alkyl (e.g. methyl, ethyl, propyl,
isopropyl, butyl, tert-butyl, etc.), hydroxy, C1-C6 alkoxy (e.g.
methoxy, ethoxy, propoxy, butoxy, etc.), halogen (e.g. fluorine,
chlorine, bromine, etc.), nitro, cyano, C1-C6 acyl(e.g. formyl,
acetyl, propionyl, etc.), C1-C6 acyloxy (e.g. formyloxy,
acetoxy, propionyloxy, etc.), mercapto, C1-C6 alkylthio (e.g.
methylthio, ethylthio, propylthio, butylthio, isobutylthio,
etc.), amino, C1-C6 alkylamino (e.g. methylamino, ethylamino,
propylamino, butylamino, etc.), di(C1-C6 alkyl)amino (e.g.
dimethylamino, diethylamino, dipropylamino, dibutylamino,
etc.), carboxyl, C2-C7 alkoxycarbonyl (e.g. methoxycarbonyl,
ethoxycarbonyl, propoxycarbonyl, etc.), amido,
trifluoromethyl, C1-C6 alkylsulfonyl(e.g. methylsulfonyl,
ethylsulfonyl, etc.), aminosulfonyl, C3-C7 cycloalkyl (e.g.

cyclopentyl, cyclohexyl, etc.). phenyl, acylamido (e.g.
acetamido, propionylamido, etc.) and the like, among which
hydroxy, C1-C6 alkyl, C1-C6 alkoxy, mercapto, C1-C6 alkylthio,
halogen, trifluoromethyl, C1-C6 acyl, C2-C7 alkoxycarbonyl and
acylamido are preferable.
A preferable example for R1 and R2 includes phenyl which
may be substituted with halo C1-C6 alkyl (e.g. trifluoromethyl,
etc.), C1-C6 alkyl (e.g. methyl, ethyl, etc.), halogen (e.g.
fluorine, chlorine, bromine, etc.), C1-C6 alkoxy (e.g. methoxy,
etc.), C1-C6 acyl (e.g. acetyl, etc.), C2-C6 alkenyl
(e.g.isopropenyl, etc.) or cyano; a preferable example for R5,
R6 and R7 includes phenyl which may be substituted with halo
C1-C6 alkyl (e.g. trifluoromethyl, etc.), C1-C6 alkyl (e.g.
methyl, etc. ), halogen (e.g. chlorine, etc. ) or C1-C6 alkoxy (e.g.
methoxy, etc.); a preferable example for R8 and R9 includes
phenyl; a preferable example for R11 and R12 includes phenyl;
a preferable example for R18 and R19 includes phenyl; a preferable
example for R43 includes biphenyl; a preferable example for ring
A includes phenyl; and preferable examples for ring C include
phenyl or naphthyl.
"C7-C16 aralkyl" refers to an arylalkyl, of which aryl
moiety is phenyl (which may be substituted with 1 to 3
substituent(s) mentioned in the above description of aryl) and
alkyl moiety is alkyl having 1 to 6 carbon atom(s). Examples
thereof include benzyl, phenethyl, phenylpropyl, phenylbutyl
or phenylhexyl, etc., among which benzyl or phenylethyl is
preferable. A preferable example for R1 and R2 includes benzyl;
a preferable example for R11 and R12 includes benzyl; and a
preferable example for ring C includes benzyl.
"C6-C14 aryloxy" refers to phenoxy, naphthyloxy, etc.
(where the phenyl group or naphthyl group may be substituted
with 1 to 3 substituent(s) mentioned in the above description
of aryl), preferably phenoxy. A preferable example for R1 and
R2 includes phenoxy, and a preferable example for R15 includes
phenoxy.
"C7-C16aralkyloxy" refers to an arylalkoxy of which alkoxy
moiety has 1 to 4 carbon atom(s) (where the aryl group may be
substituted with 1 to 3 substituent (s) mentioned in the above
description of aryl), and example thereof includes benzyloxy,
phenethyloxy, pheriylpropyloxy, phenylbutyloxy, etc.,
preferably benzyloxy. A preferable example for R1 and R2
includes benzyloxy; a preferable example for R3 includes
benzyloxy; and a preferable example for R15 includes benzyloxy.
"C7-C15 arylcarbonyl" refers to benzoyl, naphthoyl, etc.
(where the phenyl group or naphthyl group may be substituted
with 1 to 3 substituent(s) mentioned in the above description
of aryl), preferably benzoyl. A preferable example for R1 and
R2 includes benzoyl.
"C7-C15 arylcarbonylamino" refers to phenylcarbonylamino,
naphthylcarbonylamino , etc. (where the phenyl group or naphthyl
group may be substituted with 1 to 3 substituent (s) mentioned
in the above description of aryl), preferably benzoyl. A
preferable example for ring C includes phenylcarbonylamino.
"C8-C16 aralkylcarbonylamino" refers to
benzylcarbonylamino, naphthylcarbonylamino, etc. (where the
phenyl group or naphthyl group may be substituted with 1 to 3
substituent(s) mentioned in the above description of aryl),
preferably benzylcarbonylamino. A preferable example for ring
C includes benzylcarbonylamino.
"heterocycle" refers to a 5- to 6-membered heteroaromatic
ring, a 5- to 6-membered saturated heterocycle or a 5- to
6-membered unsaturated heterocycle, any of which contains 1 to
3 heteroatom(s) selected from nitrogen, oxygen and sulfur as
an atom constituting the ring other than carbon atom, or a fused
heterocyclic ring in which said heterocycle and benzene ring
are fused. Specifically, its example includes thiophen-2-yl,
thiophen-3-yl, furan-2-yl, furan-3-yl, pyrrol-1-yl,
pyrrol-2-yl, pyrrol-3-yl, imidazol-1-yl, imidazol-2-yl,
imidazol-4-yl, imidazol-5-yl, pyrazol-1-yl, pyrazol-3-yl,
pyrazol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl,
oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl,
isoxazol-4-yl, isoxazol-5-yl, pyrimidin-2-yl, pyrimidin-4-yl,
pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,
pyrrolidin-2-yl, pyrrolidin-3-yl, benzothiophen-2-yl,
benzothiophen-3-yl, benzofuran-2-yl, benzofuran-3-yl,
indol-2-yl, indol-3-yl, benzimidazol-1-yl, benzimidazol-2-yl,
benzothiazol-2-yl, benzoxazol-2-yl, quinolin-2-yl,
quinolin-3-yl, quinolin-4-yl, isoquinolin-1-yl,
isoquinolin-3-yl, isoquinolin-4-yl, 1,3,4-thiadiazol-2-yl,
morpholin-4-yl, etc.
A preferable example for R1 and R2 includes thiophen-3-yl;
preferable examples for ring A include imidazol-5-yl,
thiazol-5-yl, pyridin-3-yl or pyrrolidin-2-yl; a preferable
example for R3 includes thiazol-2-yl; and preferable examples
for ring C include pyridin-2-yl, pyridin-3-yl, thiophen-2-yl,
thiophen-3-yl or thiazol-2-yl.
With regard to a substituent in "optionally substituted

heterocycle", the same substituents as those mentioned in the
above description of aryl may be exemplified. The number of
substituents is not particularly limited so long as they are
chemically acceptable, while the number is preferably around
1 to 3.
"C2-C6 alkenyl"refers to a straight- or branched-chain
alkenyl group having 2 to 6 carbon atoms, and its example
includes vinyl, n-propenyl, isopropenyl, n-butenyl,
isobutenyl, sec-butenyl, tert-butenyl, n-pentenyl,
isopentenyl, neopentenyl, 1-methylpropenyl, n-hexenyl,
isohexenyl, 1,l-d±methylbutenyl, 2,2-dimethylbutenyl,
3,3-dimethylbutenyl, 3,3-dimethylpropenyl, 2-ethylbutenyl,
etc. A preferable example for R2 and R2 includes n-propenyl,
and a preferable example for D includes n-propenyl.
prodrug" of the compound refers to a derivative of the
compound of the present invention, which has a group capable
of being chemically or metabolically converted and shows
pharmaceutical activity after it is hydrolyzed or solvolyzed
or converted under physiological conditions.
For example, there may be listed a derivative in which
a substituent such as -CO-C1-C6 alkyl, -CO2-C1-C6 alkyl,
-CONH-C1-C6 alkyl, -CO-C2-C6 alkenyl, -CO2-C2-C6 alkenyl,
-CONH-C2-C6 alkenyl, -CO-C6-C14 aryl, -CO2-C6-C14 aryl,
-CONH-C6-C14 aryl, -CO-heterocycle, -C02-heterocycle,
-CONH-heterocycle, etc. (wherein any of said C1-C6 alkyl, C2-C6
alkenyl, C6-C14 aryl and heterocycle may be substituted with
halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, carboxyl, amino,
amino acid residue, -PO3H2, -SO3H, -CO-polyethyleneglycol
residue, -C02-polyethyleneglycol residue.

-CO-polyethyleneglycol monoalkyl ether residue or
-C02-polyethyleneglycol monoalkyl ether residue) is attached
to the hydroxy group of the compound.
Also, there may be exemplified a derivative in which a
substituent such as -CO-C1-C6 alkyl, -CO2-C1-C6 alkyl, -CO-C2-C6
alkenyl, -CO2-C2-C6 alkenyl, -CO2-C6-C14 aryl, -CO-C6-C14 aryl,
-CO-heterocycle, -CO2-heterocycle, etc. (wherein any of said
C1-C6 alkyl, C2-C6 alkenyl, C6-C14 aryl and heterocycle may be
substituted with halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
carboxyl, amino, amino acid residue, -PO3H2, -SO3H,
-CO-polyethyleneglydol residue, -C02-polyethyleneglycol
residue, -CO-polyethyleneglycol monoalkyl ether residue,
-CO2-polyethyleneglycol monoalkyl ether residue or -PO3H2,
etc.) is attached to the amino group of the compound.
Furthermore, there may be exemplified a derivative in
which a substituent such as C1-C6 alkoxy, C6-Cl4 aryloxy, etc.
(wherein said C1-C6 alkoxy or C6-C14 aryloxy may be substituted
with halogen, C1-C6 alkyl, hydroxy, C1-C6 alkoxy, carboxyl, amino,
amino acid residue, -PO3H2, -SO3H, polyethyleneglycol residue
or polyethyleneglycol monoalkyl ether residue, etc.) is
attached to the carboxyl group of the compound.
"Pharmaceutically acceptable salt" includes various
inorganic acid addition salts such as hydrochloride,
hydrobromide, sulphate, phosphate or nitrate, etc.; various
organic acid addition salts such as acetate, propionate,
succinate, glycolate, lactate, malate, oxalate, tartrate,
citrate, maleate, fumarate, methanesulfonate, benzensulfonate,
p-toluenesulfonate or ascorbate, etc.; or various salts with
an amino acid such as aspartate or glutamate, etc. , although
it is not limited thereto. It may be hydrated compound, hydrate
or solvate depending on the circumstances.
"MTP in the small intestine" refers to the MTP existing
in small intestinal epithelial cells.
"MTP in the liver" refers to the MTP existing in hepatic
cells.
The expression "selectively inhibit MTP in the small
intestine" means the level of inhibition is at least about 5
times higher, preferably about 10 times higher, than MTP
inhibition in other parts of body such as liver and heart,
especially liver. To be more specific, on the basis of S9
metabolic stability test, it means that in the test using human
or hamster S9 the remaining rate of unaltered form 10 minutes
after the treatment with small intestine S9 is about 10 times
or more higher than that in the case of the treatment with liver
S9 (see Test Example 7).
The expression "it is metabolized to the amount at which
the remaining MTP inhibitor in the liver does not substantially
inhibit the MTP in the liver" means that almost all of the orally
administered MTP inhibitors are metabolized to an inactive
metabolite before arriving at the liver or at the moment of
arriving at the liver and show substantially no MTP inhibitory
activity in the liver, i.e. the MTP inhibitors are converted
to those that do not substantially inhibit TG release from the
liver. More specifically, it means the condition where
TG-releasing activity of the liver is kept at the level of about
80% or more, preferably about 90% or more, more preferably 100%
of the normal level. In terms of metabolism, it means that the
ratio of inactive metabolite to unaltered form in portal vein
blood is approximately 8 or more to 1 one hour after the oral
administration to hamsters, i.e. about 80% or more of the agent
(compound) is metabolized before arriving at the liver (see Test
Example 6), or on the basis of liver S9 metabolic stability test,
it means that 10 minutes after the test using human or hamster
S9 the remaining rate of unaltered form is about 20% or less,
preferably about 10% or less, more preferably about 8% or less
(see Test Example 7).
The expression "MTP inhibitor does not substantially
inhibit MTP in the liver" has essentially the same meaning with
the above "it is metabolized to the amount at which the remaining
MTP inhibitor in the liver does not substantially inhibit the
MTP in the liver", and means the condition where TG-releasing
activity of the liver is kept at the level of about 80% or more,
preferably about 90% or more, more preferably 100% of the normal
level.
As "pharmaceutically acceptable carrier", various
organic or inorganic carrier materials which are conventionally
used as formulation material are used, and it is formulated as
excipient, lubricant, binder, disintegrating agent, solvent,
solubilizer, suspending agent, isotonizing agent, buffer,
soothing agent, etc. If desired, pharmaceutical additives
such as preservative, antioxidant, coloring agent, sweetening
agent, etc. may be also used. Preferable examples of said
excipient include lactose, sucrose, D-mannitol, starch,
crystalline cellulose, light anhydrous silicic acid, etc.
Preferable examples of said lubricant include magnesium
stearate, calcium stearate, talc, colloidal silica, etc.
Preferable examples of said binder include crystalline
cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl
cellulose, hydroxypropyl methylcellulose,
polyvinylpyrrolidone, etc. Preferable examples of said
disintegrating agent include starch, carboxymethylcellulose,
carboxymethylcellulose calcium, crosscarmellose sodium,
sodium carboxymethylstarch, etc. Preferable examples of said
solvent include water for injection, alcohol, propylene glycol,
macrogol, sesame-seed oil, corn oil, propylene glycol fatty
acid ester, etc. Preferable examples of said solubilizer
include polyethyleneglycol, propyleneglycol, D-mannitol,
benzyl benzoate, ethanol, trisaminomethane, cholesterol,
triethanolamine, sodium carbonate, sodium citrate, etc.
Preferable examples of said suspending agent include
surfactants (e.g. stearyl triethanolamine, sodium lauryl
sulfate, lauryl aminopropionic acid, lecithin, benzalkonium
chloride, benzethonium chloride, glycerin monostearate, etc),
polyvinyl alcohol, polyvinylpyrrolidone,
carboxymethylcellulose sodium, methylcellulose,
hydroxymethyl cellulose, etc. Preferable examples of said
isotonizing agent include sodium chloride, glycerin,
D-mannitol, etc. Preferable examples of said buffer include
phosphate, acetate, carbonate, citrate, etc. Preferable
examples of said soothing agent include benzyl alcohol, etc.
Preferable examples of said preservative include
paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol,
phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.
Preferable examples of said antioxidant include sulfites,
ascorbic acid, etc. Preferable examples of said sweetening
agent include aspartame, saccharin sodium, stevia, etc.
Preferable examples of said coloring agent include food colors
such as food yellow No. 5, food red No. 2 and food blue No. 2,
lake colors for food, iron oxide, etc.
Best mode for carrying out the invention
Detailed description is given below with respect to
various substituents.
R1 is preferably hydrogen; C1-C6 alkyl such as methyl,
ethyl, etc.; C1-C6 alkoxy such as methoxy, isopropoxy, etc.;
halogen such as fluorine, chlorine, etc. ; halo C1-C6 alkyl such
as trifluoromethyl, etc. ; or C2-C6 alkenyl such as isopropenyl,
etc.
R2 is preferably phenyl (which may be substituted with
halo C1-C6 alkyl such as trifluoromethymethyl, etc. ; C1-C6 alkyl
such as methyl, ethyl, etc.; halogen such as fluoro, chlorine,
bromine, etc.; C1-C6 alkoxy such as methoxy, etc.; C1-C6 acyl
such as acetyl, etc. ; C2-C6 alkenyl such as isopropenyl, etc. ;
or cyano); C1-C6 alkyl such as ethyl, isopropyl, etc.; C3-C7
cycloalkyl such as cyclohexyl, etc. ; C1-C6 alkoxy such as butoxy,
etc. ; halo C1-C6 alkyl such as trifluoromethyl, etc.; halo C1-C6
alkyloxy such as trifluoromethoxy, etc.; C7-C16 aralkyl such as
benzyl, etc.; C6-C14 aryloxy such as phenoxy (of which aryl
moiety may be substituted with halo C1-C6 alkyl such as
trifluoromethyl, etc.), etc.; C7-C15 arylcarbonyl such as
benzoyl (of which aryl moiety may be substituted with halogen
such as chlorine, etc.), etc.; heterocycle such as
thiophen-3-yl, etc.; C2-C7 alkoxycarbonyl such as
butoxycarbonyl, etc.; -N(R40) (R41) (wherein R40 and R41 are each
independently hydrogen or optionally substituted phenyl).
R2 is preferably hydrogen or halogen such as chlorine,
etc.
R2 is preferably hydrogen, halo C1-C6 alkyl such as
trifluoromethyl, etc.; C1-C6 alkyl such as methyl, ethyl, etc. ;
halogen such as fluorine, chlorine, bromine, etc.; C1-C6 alkoxy
such as methoxy, etc. ; C1-C6 acyl such as methylcarbonyl, etc. ;
C2-C6 alkenyl such as isopropenyl, etc.; or cyano.
Ring A is preferably

among which phenyl is especially preferred.
X is preferably -COO-, -N(R10)CO- or -CON(R10)- (wherein
R10 is hydrogen; C1-C6 alkyl such as methyl, isopropyl, etc.;
or C3-C7 cycloalkyl such as cyclohexyl, etc. ) , among which -COO-
or -CONH- is especially preferred.
Ring B is preferably
R3 is preferably hydrogen; hydroxy; halogen such as
chlorine, bromine, etc.; C1-C6 alkyl such as methyl, ethyl,
isopropyl, isobutyl, etc.; substituted C1-C6 alkyl such as
isobutyl substituted with hydroxy, etc.; C1-C6 alkoxy such as
methoxy, ethoxy, propoxy, isopropoxy, etc.; halo Ci-C6 alkyl
such as trif luoromethyl, etc.; C7-C16 aralkyloxy such as
benzyloxy, etc.; C1-C6 acyl such as formyl, etc.; optionally
substituted heterocycle such as 4-methyl-thiazol-2-yl, etc.;
-CON(R11) (R12) (wherein R11 and R12 are each independently
hydrogen; C1-C6 alkyl such as methyl, ethyl, propyl, isopropyl,
etc.; C6-C14 aryl such as phenyl, etc.; C7-C16 aralkyl such as
benzyl, etc.; C1-C6 alkoxy such as methoxy, etc.; or R11 and R12
may be taken together with the nitrogen to form
(wherein p is an integer of 0 or 1)); -N(R13)(R14) or
-CH2-N(R13) (R14) (wherein R13 and R14 are each independently
hydrogen; C1-C6 alkyl such as methyl, ethyl, etc.; C2-C7
alkoxycarbonyl such as methoxycarbonyl, etc.; C1-C6 acyl such
as acetyl, etc.; or R13 and R14 may be taken together with the
nitrogen to which they are attached to form

(wherein p has the same meaning as defined above)); or -CO(R15)
(wherein R15 is C1-C6 alkyl such as isopropyl, etc. ; C1-C6 alkoxy
such as methoxy, ethoxy, propoxy, isopropoxy, etc.; C7-C16
aralkyloxy such as benzyloxy, etc.; or hydroxy).
Alternatively, R3 and R10 may be taken together with the nitrogen
to which R10 is attached and ring B to form

R4 is preferably hydrogen or halogen such as fluorine,
chlorine, bromine, etc.
Alkl1 is preferably methylene or ethane-1,1-diyl.
1 is preferably 0, 1 or 2.
Alkl2 is preferably methylene.
m is preferably 0 or an integer of 1 to 3.
D is preferably C1-C6 alkyl such as ethyl, propyl,
isopropyl, butyl, isobutyl, sec-butyl, sec-pentyl, etc.; C2-C6
alkenyl such as n-propenyl, etc.; C2-C7 alkoxycarbonyl such as
ethoxycarbonyl, etc.; -N(R42) -CO(R43) (wherein R42 is hydrogen
or C1-C6 alkyl; R43 is C6-C14 aryl such as biphenyl, etc. ; or C7-C15
aralkyl); or a group of the formula shown below:

(wherein ring C, R5, R6 and R7 each has the same meaning as defined
above).
Ring C is preferably C6-C14 aryl such as phenyl, naphthyl,
etc.; C3-C7 cycloalkyl such as cyclopentyl, cyclohexyl, etc.;
C7-C16 aralkyl such as benzyl, etc.; or heterocycle such as
pyridine-3-yl, thiophen-3-yl, thiazol-2-yl, etc.
Alternatively, ring C may be take together with R7 and R8 to
form

R5 is preferably hydrogen; C1-C6 alkyl such as methyl,
etc.; C1-C6 alkoxy such as methoxy, etc.; halogen such as
chlorine, etc.; nitro; amino; C6-C14 aryl such as phenyl, etc.;
or -CON(R16) (R17) or -CH2-CON(R16) (R17) (wherein R16 and R17 are
each independently hydrogen; C1-C6 alkyl such as ethyl, etc.,
or halo-C1-C6 alkyl such as 2,2,2-trifluoroethyl, etc.).
R6 is preferably hydrogen or halogen such as chlorine,
etc.
R7 is preferably hydrogen.
R8 and R9 are each independently preferably hydrogen; C1-C6
alkyl such as ethyl, etc.; C6-C14 aryl such as phenyl, etc.;
hydroxy-C1-C6 alkyl such as hydroxymethyl, etc.;
-CON(R18) (R19) (wherein R18 and R19 are each independently
hydrogen; C1-C6 alkyl such as methyl, ethyl, propyl, isopropyl,
butyl, isobutyl, etc.; C3-C7 cycloalkyl such as cyclohexyl,
etc.; halo C1-C6 alkyl such as 2,2,2- trifluoroethyl, etc.;
C2-C12 alkoxyalkyl such as methoxyethyl, etc. ; or C6-C14 aryl such
as phenyl, etc.); -COO(R20) or - (CH2)n-OCO(R20) (wherein R20 is
hydrogen; C1-C6 alkyl such as methyl, ethyl, propyl, isopropyl,
isobutyl, etc.; or C3-C7 cycloalkyl such as cyclohexyl, etc.,
and n is an integer of 0 or 1); -N(R21) (R22) (wherein R21 and R22
are each independently hydrogen; C1-C6 alkyl such as methyl,
isopropyl, etc.; C1-C6 acyl such as acetyl, propionyl, butyryl,
etc.; C1-C6 alkylsulfonyl such as methylsulfonyl, etc.; or R21
and R22 may be taken together with the nitrogen atom to which
they are attached to form

or R8 and R9 taken together may form C3-C7 cycloalkyl such as
cyclopropyl, cyclohexyl, etc.
Preferred embodiments of various substituents and the
substitution site will be illustrated below.
R1 is preferably hydrogen, halo C1-C6 alkyl or C1-C6 alkyl,
among which hydrogen is especially preferred.
R2 is preferably phenyl (which may be substituted with
halo C1-C6 alkyl such as trif luoromethyl, etc.; C1-C6 alkyl such
as methyl, etc.; halogen such as chlorine, etc.; or C1-C6 alkoxy
such as methoxy, etc.).
R2 is preferably hydrogen.
R2 is preferably hydrogen, halo-C1-C6 alkyl, halogen,
C1-C6 alkyl or C1-C6 alkoxy, and trif luoromethyl is especially
preferred.
X is preferably -COO- or -CON(R10)- (R10 has the same
meaning as defined above), among which -CONH- is especially
preferred.
Ring B is preferably phenyl.
R3 is preferably C1-C6 alkyl, C1-C6 alkoxy, -CON(R11) (R12)
(wherein R11 and R12 are each independently preferably hydrogen
or C1-C6 alkyl) or -CO(R15) (wherein R15 is preferably C1-C6
alkoxy).
R4 is preferably hydrogen or methyl, and especially
preferably methyl.
Alk1 is preferably methylene.
Alk2 is preferably methylene.
1 is preferably 0 or 1, especially 1.
m is preferably 1 or 2, especially 1 or 2.
D is preferably C1-C6 alkyl or a group of the formula shown
below:
(wherein ring C, R5 , R6 and R7 each has the same meaning as defined
above).
Ring C is preferably phenyl, pyridin-3-yl, thiophen-3-yl,
thiophen-2-yl and thiazol-2-yl, among which phenyl is
especially preferred.
R5, R6 and R7 each is preferably hydrogen, halogen or C1-C6
alkyl, among which hydrogen is especially preferred.
R8 and R9 each is preferably hydrogen, C1-C6 alkyl, C6-C14
aryl, -CON(R18) (R19) (wherein R18 and R19 each is preferably
hydrogen or C1-C6 alkyl) or -COO(R20) (wherein R20 is preferably
hydrogen or C1-C6 alkyl) , among which -CON(R18) (R19) (wherein R18
and R19 each is preferably hydrogen or C1-C6 alkyl) or
-COO(R20) (wherein R20 is preferably hydrogen or C1-C6 alkyl) are
more preferred, and -COO(R20) (wherein R20 is preferably C1-C6
alkyl) is especially preferred.
The substitution site of -(CH2)1- on the benzene ring in
the formula (1') is preferably i-position.
The compounds of the present invention may include
hydrates or solvates, depending on the case, and may further
include their metabolites. Furthermore, the compounds of the
present invention include racemates and optically active
compounds. The optically active compounds are preferably
those wherein one of enantioraers is in enantiomer excess of

about 90% or higher, more preferably in enantiomer excess of
about 99% or higher.
When the compounds of the present invention are used as
an agent for the treatment or prophylaxis of hyperlipidemia or
arteriosclerosis, they can be administered systemically or
locally, and orally or parenterally. Though the dose may vary
depending on the age, body weight, symptoms, therapeutic effect,
etc. , the daily dose per adult is in the range of 0.1 mg to lg
per one dose and can be administered one to several times per
day. Also, the compounds of the present invention can be
administered to human beings as well as animals other than human
beings, especially mammals, for the treatment or prevention of
said diseases. The compounds of the present invention can be
used in the same way for the treatment or prevention of coronary
artery diseases, obesity, diabetes or hypertension.
In the formulation of the compounds of the present
invention into solid compositions and liquid compositions for
oral administration or injections, etc., for parenteral
administration, there may be added appropriate additives such
as diluents, dispersants, adsorbents, solubilizers, etc. In
addition, the composition of the present invention may take the
known form such as tablets, pills, powders, granules,
suppositories, injections, eye drops, solutions, capsules,
troches, aerosols, elixirs, suspensions, emulsions, syrups,
etc.
When the compounds of the present invention are
formulated into solid preparations such as tablets, pills,
powders, granules, etc., examples of such an additive include

lactose, mannitol, glucose, hydroxypropyl cellulose
microcrystalline cellulose, starch, polyvinylpyrrolidone,
magnesium aluminometasilicate or powdery silicic anhydride.
In the case where the compounds of the present invention are
formulated into tablets or pills, they may be coated with a
gastroenteric or enteric coating film containing a substance
such as sucrose, gelatin, hydroxypropyl cellulose or
hydroxymethyl cellulose phthalate. Furthermore, the tablets or
pills may be multi-layered tablets comprising two or more
layers.
As the pharmaceutical compositions of the present
invention, there are also exemplified capsules in which are
filled liquid, semi-solid or solid contents prepared by
dissolving the compounds of the present invention in a solvent
and adding an additive thereto. Examples of said solvents are
purified water, ethanol, vegetable oil, etc., among which
ethanol or a mixture of purified water and ethanol is preferably
used. Any additives commonly used in the preparation of
capsules can be used without any particular limitation. Such
additives include, for example, propylene glycol fatty acid
esters; low molecular weight polyethylene glycols such as
polyethylene glycol 200 to 600, etc., glycerine fatty acid
esters thereof, and medium chain fatty acid triglycerides
thereof; alcohols/polyols such as stearyl alcohol, cetanol,
polyethylene glycol, etc., or esters thereof; lipids such as
sesame oil, soy bean oil, peanut oil, corn oil, hydrogenated
oil, paraffin oil, bleached wax; fatty acids such as triethy1
citrate, triacetin, stearic acid, palmitic acid, myristic acid,
etc., and derivatives thereof. These additives are suitable

for preparing liquid or semi-solid contents. In the capsules
of the present invention, propylene glycol fatty acid esters
are preferable as such an additive. Examples of the propylene
glycol fatty acid esters are propylene glycol monocaprylate
(Capmul PG-8 (Brand name), Sefol 218 (Brand name), Capryo 190
(Brand name), propylene glycol monolaurate (Lauroglycol FCC
(Brand name) , propylene glycol monooleate (Myverol P-06 (Brand
name)), propylene glycol myristate, propylene glycol
monostearate, propylene glycol lisinolate (Propymuls (Brand
name)), propylene glycol dicaprylate/dicaprate (Captex
(Trademark) 200 (Brarid name)) propylene glycol dilaurate,
propylene glycol distearate and propylene glycol dioctanoate
(Captex (Trademark) 800 (Brand name)). Although there is no
particular limitation to the materials constituting the
capsules of the present invention, they include, for example,
polysaccharides derived from natural products such as agar,
alginic acid salt, starch, xanthan, dextran, etc; proteins such
as gelatin, casein, etc.; chemically processed products such
as hydroxystarch, pullulan, hydroxypropyl cellulose,
hydroxypropyl methylcellulose, polyvinyl alcohol or
derivatives thereof, polyacryl derivatives,
polyvinylpyrrolidone or derivatives thereof, polyethylene
glycol, etc.
In the case where the pharmaceutical compositions of the
present invention are liquid formulations for oral
administration such as pharmaceutically acceptable emulsions,
solubilizers, suspensions, syrups or elixirs, etc., diluents
to be used include, for example, purified water, ethanol,
vegetable oils, emulsifiers, etc. In addition to such diluents ,
auxiliary agents such as wetting agents, suspending agents,
sweeteners, condiments, flavors or antiseptics may be added to
said liquid formulations.
In the case where the pharmaceutical compositions of the
present invention are parenteral formulations such as
injections, there are employed sterilized aqueous or
non-aqueous solutions, solubilizers, suspending agents,
emulsifiers, etc. Examples of the aqueous solutions,
solubilizers and suspending agents include distilled water for
injections, physiological saline, cyclodextrin, and
derivatives thereoff organic amines such as triethanolamine,
diethanolamine, monoethanolamine, triethylamine, etc.; and
inorganic alkaline solutions. When aqueous solutions are
employed, for example, propylene glycol, polyethylene glycol
or vegetable oils such as olive oil, or alcohols such as ethanol
may be further added. Further, surfactants (for mixed micelle
formation) such as polyoxyethylene hydrogenated castor oils,
sucrose fatty acid esters, or lecithin or hydrogenated lecithin
(for liposome formation), etc. can be used as a solubilizer.
Furthermore, with regard to the parenteral formulations of the
present invention, they may be formulated into emulsions
comprising non-aqueous solubilizers such as vegetable oils,
together with lecithin, polyoxyethylene hydrogenated castor
oil or polyoxyethylene-polyoxypropylene glycol, etc.
Further, the present invention provides a novel agent for
the treatment or prophylaxis of hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension with new functions that have never been known
before. The agents of the present invention for the treatment

or prevention of said diseases are characterized in that they
selectively inhibit MTP (microsomal triglyceride transfer
protein) in the small intestine. Among these agents, an agent
which does not substantially inhibit MTP in the liver, while
inhibits only MTP in the small intestine is desirable.
Specifically, it is preferable that MTP inhibition of the agent
in the liver is approximately 1/3 or less, preferably 1/100 or
less when compared to that in the small intestine as estimated
in terms of ED50 or ED2o- As one preferred embodiment of the
therapeutic or prophylactic agents of the present invention for
said diseases, they inhibit MTP in the small intestine, and they
are then metabolized in the small intestine, blood, and liver
to the amount at which the residual agent arriving at the liver
does not substantially inhibit MTP in the liver. It is
particularly preferable that, when 300mg/kg of the compound of
the present invention is administered orally, the rate of liver
TG release inhibition exerted by the residual compound reaching
the liver is about 20% or less, preferably less than about 10%,
more preferably about 0%. Specifically, it is desirable that
the agent has about 40% or less, preferably about 20% or less
inhibition rate of liver TG release when assayed by the method
of Test Example 4 which will be hereinafter mentioned.
The pharmaceutical compositions or agents of the present
invention can be used in combination with other pharmaceutical
compositions or agents. As other agents, there may be
exemplified drugs for the treatment or prophylaxis of
hyperlipidemia, arteriosclerosis, coronary artery disease,
obesity, diabetes, or hypertension, and they can be used solely

or in combination with two or more kinds of said drugs . Examples
of the antihyperlipidemic drugs include a statin-type drug,
more specifically, lovastatin, simvastatin, pravastatin,
fluvastatin, atorvastatin or cerivastatin. Examples of the
anti-obesity drugs include mazindol or olristat. Examples of
the anti-diabetic drugs include insulin preparations,
sulfonylurea drugs, insulin secretion-promotor drugs,
sulfonamide drugs, biguanide drugs, a-glucosidase inhibitors,
insulin resistance-improving drugs, etc., more specifically
insulin, glibenclamid, tolbutamide, glyclopyramide,
acetohexamide, glimepiride, tolazamide, gliclazide,
nateglinide, glibuzol, metformin hydrochloride, buformin
hydrochloride, voglibose, acarbose, pioglitazone
hydrochloride, etc. Examples of the anti-hypertension drugs
include loop diuretics, angiotensin converting enzyme
inhibitors, angiotensin II receptor antagonists. Calcium
antagonists, b-blockers, a,b-blockers and a-blockers , and more
specifically, furosemide delayed release, captopril,
captopril delayed release, enalapril maleate, alacepril,
delapril hydrochloride, silazapril, lisinopril, benazepril
hydrochloride, imidapril hydrochloride, temocapril
hydrochloride, quinapril hydrochloride, trandolapril,
perindopril erbumine, losartan pota$sium, candesartan
cilexetil, nicardipine hydrochloride, nicardipine
hydrochloride delayed release, nilvadipine, nifedipine,
nifedipine delayed release, benidipine hydrochloride,
diltiazem hydrochloride, diltiazem hydrochloride delayed
release, nisoldipine, nitrendipine, manidipine hydrochloride,
barnidipine hydrochloride, efonidipifie hydrochloride,
amlodipine besylate, felodipine, cilnidipine, aranidipine,
propranolol hydrochloride, propranolol hydrochloride delayed
release, pindolol, pindolol delayed release, indenolol
hydrochloride, carteolol hydrochlbride, carteolol
hydrochloride delayed release, bunitrdlol hydrochloride,
bunitrolol hydrochloride delayed Release, atenolol,
asebutolol hydrochloride, metoprolol tartrate, metoprolol
tartrate delayed release, nipradilol, penbutolol sulfate,
tilisolol hydrochloride, carvedilol, bisoprolol fumarate,
betaxolol hydrochloride, celiprolol hydrochloride, bopindolol
malonate, bevantoloir hydrochloride, labetalol hydrochloride,
arotinolol hydrochloride, amosulalol hydrochloride, prazosin
hydrochloride, terazosin hydrochloride, doxazosin mesylate,
bunazocin hydrochloride, bunazocin hydrochloride delayed
release, urapidil, and phentolamine mesylate, etc.
There is no particular limitation to the timing for the
administration of pharmaceutical compositions or agents and
other drugs for combination use according to the present
invention, and they may be administered simultaneously or
intermittently.
The amount of such drugs for combination use can be
determined based on their clinical doses, and can be chosen
depending on the age, weight, condition, medication time,
dosage form, method of administration, combination, etc.
There is no particular limitation to the dosage form of the drugs
for combination use, and it may be sufficient that the
pharmaceutical compositions or agents and other drugs for
combination use according to the present invention are combined
at the time of administration.
Next, a process for preparing an ester compound
represented by the formula (1) will be illustrated below as an
example, but the process of the present invention is not limited
thereto. In the process mentioned below, D is a group of the
formula (2):

(wherein ring C, R5, R6 and R7 each has the same meaning as defined
above), and when D is C1-C6 alkyl, C2-C6 alkenyl, C2-C7
alkoxycarbonyl or -N(R42) -CO(R43) (R42 and R43 each has the same
meaning as defined above), the compound can be prepared in the
same.
In addition, the functional groups other than those to
be reacted may be optionally protected in a previous stage and
may be deprotected in an appropriate stage.
Further, the reaction in each step may be carried out in
the usual manner, and separation and purification may be
conducted by the appropriate selection or combination of
conventional methods such as crystallization,
recrystallization, column chromatography, preparative HPLC,
etc.
Process 1
Among the compounds represented by the formula (1), a
process for preparing compounds in which X is -CONH-(CH2)n-
will be illustrated below.
In the above reaction scheme, R1, R2, R3, R4, R5, R6, R7,
R8, R9, 1, m, n, Alk1, Alk2, ring A, ring B, and ring C each has
the same meaning as defined above and R23 is C1-C6 alkyl.

Step 1-1
A carboxylic acid of the formula (2) is reacted with oxalyl
chloride or thionyl chloride in a solvent to give an acid
chloride of the formula (3).
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and esters such as
ethyl acetate, methyl acetate, butyl acetate, etc., and they
may be used solely or in combination thereof. Preferred
solvents in the present reaction include methylene chloride,
chloroform or toluene, all of which contain a catalytic amount
of N,N-dimethylformamide.
The reaction temperature is about -20°C to 120°C,
preferably about 0°C to room temperature.
The reaction time is about 10 minutes to 8 hours,
preferably about 30 minutes to 4 hours.
Step 1-2
This step is a general reduction process for the nitro
group attached directly to the aromatic ring. A nitro compound
of the formula (4) is hydrogenated in a solvent in the presence
of a catalyst to give a compound of the formula (5).
The solvent used in the reaction includes, for example,
ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane,
etc.; alcohols such as methanol, ethanol, isopropyl alcohol,
t-butanol, etc.; and esters such as ethyl acetate, methyl
acetate, butyl acetate, etc.; and they are used solely or in
combination thereof. Preferred solvents in the present
reaction include alcohols such as methanol, ethanol, isopropyl
alcohol, t-butanol, etc., and a mixture of said alcohol solvent
and tetrahydrofuran and/or water.
The catalyst used in the reaction includes, for example,
palladium-carbon, palladium hydroxide, Raney-Ni, platinum
oxide, and among which palladium-carbon or reduced iron is
preferred.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 100°C.
The reaction time is about 30 minutes to 8 days , preferably
about one hour to 96 hours.
Step 1-3
This step is a general condensation reaction between acid
chlorides and amines. An acid chloride of the formula (3) is
condensed with an amine of the formula (5) in a solvent in the
presence of a base to give a compound of the formula (6) .
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and esters such as
ethyl acetate, methyl acetate, butyl acetate, etc., and they
can be used solely or in combination thereof. Preferred
solvents in the present reaction include methylene chloride,
chloroform, toluene, ethyl acetate or tetrahydrofuran.
Examples of the bases used in the present invention
include organic bases such as triethylamine, pyridine.
N-methylmorpholine, etc.; alkali metal hydroxides such as
lithium hydroxide, sodium hydroxide, potassium hydroxide,
etc.; and alkali metal carbonates such as sodium carbonate,
potassium carbonate, sodium bicarbonate, potassium
bicarbonate, etc., among which triethylamine, sodium hydroxide
or sodium bicarbonate is preferable.
The reaction temperature is about 0°C to 80°C, preferably
about 0°C to room temperature.
The reaction time is about 10 minutes to 48 hours,
preferably about 30 minutes to 24 hours.
In the case of^a compound of the formula (5) wherein R23
is hydrogen, a compound of the formula (7) can be prepared by
one step of condensation between an aminocarboxylic acid and
an acid chloride (Schotten-Baumann reaction).
Alternatively, a compound of the formula (6) can be
prepared by using a condensing agent (e.g. WSC-HOBT, DCC-HOBT)
for a compound of the formula (2) and a compound of the formula
(5). Further, a compound of the formula (6) may be provided
by converting a compound of the formula (2) into its mixed
anhydride, followed by the reaction in the presence of a base.
Step 1-4
This step is a general ester hydrolysis reaction using
alkali . A compound of the formula ( 6 ) is hydrolysed in a solvent
in the presence of a base to give a compound of the formula (7) .
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; and alcohols such as
methanol, ethanol, isopropyl alcohol, etc.; and they can be used
solely or in combination thereof. Preferred solvents in the

present reaction include a mixture of tetrahydrofuran and
ethanol or methanol. Examples of the bases are aqueous
solutions of alkali metal carbonates such as sodium carbonate,
potassium carbonate, etc. , or aqueous solutions of alkali metal
hydroxides such as lithium hydroxide, sodium hydroxide,
potassium hydroxide, etc., among which sodium hydroxide or
lithium hydroxide is preferable.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 80°C.
The reaction time is about 1 hour to 24 hours, preferably
about 2.5 hours to 12 hours.
Step 1-5
This step is a general condensation reaction of a
carboxylic acid with an alcohol.
A carboxylic acid of the formula (7) is condensed with
an alcohol of the formula (8) in a solvent in the presence of
a base and a condensing agent to give a compound of the formula
(1-1) which is one of the objective compounds.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; esters such as ethyl
acetate, methyl acetate, butyl acetate, etc.; polar solvents
such as acetone, N,N-dimethylformamide, dimethyl sulfoxide,
etc.; and they can be used solely or in combination thereof.
Preferred solvents in the present reaction include
tetrahydrofuran, acetone, methylene chloride or
N,N-dimethylformamide.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which dimethylaminopyridine
is preferred.
Examples of the condensing agents used in the reaction
include 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride (WSC.HC1), dicyclohexylcarbodiimide (DCC), etc.
among which l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride is preferred.
The reaction temperature is about 0°C to 80°C, preferably
about 0°C to room temperature.
The reaction time is about 1 hour to 48 hours, preferably
about 3 hours to 24 hours.
As an alternative process, a carboxylic acid of the
formula (7) may be converted into its mixed anhydride and then
reacted with an alcohol of the formula (8) in the presence of
a base.
Process la
Process la as shown below is an alternative of Process
1.
In the above reaction scheme, R1, R2, R3, R4, R5, R6, R7,
R8, R9, R23, 1, m, n, Alk1, Alk2, ring A, ring B and ring C each
has the same meaning as defined above.
Step la-1
A compound of the formula (105) can be prepared from a
compound of the formula (4) in a similar manner to Step 1-4 of
Process 1.
Step la-2
A compound of the formula (106) can be prepared by
condensing a carboxylic acid of the formula (105) with an
alcohol of the formula (8) in a similar manner to Step 1-5 of
Process 1.
Step la-3
A compound of the formula (107) can be prepared from a
compound of the formula (106) in a similar manner to Step 1-2
of Process 1.
Step la-4
A compound of the formula (1-1) which is one of the
objective compounds can be prepared by condensing an amine of
the formula (107) with an acid chloride of the formula (3) in
a similar manner to Step 1-3 of Process 1.
Process 2
Among the compounds represented by the formula (1), a
process for preparing compounds in which X is -COO-(CH2)n- will
be illustrated below.
Step 2-1
This step is a condensation reaction of a carboxylic acid
with an alcohol similar to Step 1-5 of Process 1. A compound
of the formula (10) can be prepared by condensing a carboxylic
acid of the formula (9) with an alcohol of the formula (8) in
a solvent in the presence of a base and a condensing agent.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as! methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; esters such as ethyl
acetate, methyl acetate, butyl acetate, etc.; polar solvents
such as acetone, N,N-dimethylformamide, dimethyl sulfoxide,
water, etc.; and they can be used solely or in combination
thereof. Preferred solvents in the present reaction include
tetrahydrof uran, methylene chloride or N,N-dimethylformamide.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which dimethylaminopyridine
is preferred.
Examples of the condensing agents used in the reaction
include 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride (WSC-HC1), dicyclohexylcarbodiimide (DCC), etc.,
among which 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride is preferred.
The reaction temperature is about 0°C to 80°C, preferably
about 0°C to room temperature.
The reaction time is about 2 hours to 48 hours, preferably
about 6 hours to 24 hours.
Step 2-2
This step is a general deprotection method for hydroxy
groups. For example, when R24 is benzyl in a compound of the
formula (10), the compound of the formula (10) is hydrogenated
in a solvent in the presence of a catalyst to give a compound
of the formula (11).
The solvent used in the reaction includes, for example,
ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane,
diglyme, etc.; alcohols such as methanol, ethanol, isopropyl
alcohol, t-butanol,"etc.; and esters such as ethyl acetate,
methyl acetate, butyl acetate, etc.; and they can be used
solely or in combination thereof. Preferred solvents in the
present reaction are alcohols such as methanol, ethanol,
isopropyl alcohol, t-butanol, etc.
Examples of the catalyst used in the reaction include
palladium carbon, palladium hydroxide, Raney-Ni, platinum
oxide, etc., among which palladium carbon is preferred.
The reaction temperature is about 0°C to 80°C, preferably
about 0°C to room temperature.
The reaction time is about 1 hour to 16 hours, preferably
about 2 hours to 8 hours.
Step 2-3
This step is a condensation reaction between a carboxylic
acid and an alcohol similar to Step 1-5 of Process 1. A compound
of the formula (11) is condensed with an alcohol of the formula
(2) in a solvent in the presence of a base and a condensing agent
to give a compound of the formula (1-2) which is one of the
objective compounds.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; esters such as ethyl
acetate, methyl acetate, butyl acetate, etc.; and polar
solvents such as acetone, N,N-dimethylformamide, dimethyl
sulfoxide, etc. , and they can be used solely or in combination
thereof. Preferred solvents in the present reaction are
tetrahydrofuran, methylene chloride, dimethylformamide, etc.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which dimethylaminopyridine
is preferred.
Examples of the condensing agents used in the reaction
include 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride (WSC.HC1), dicyclohexylcarbodiimide (DCC), etc.,
among which l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride is preferred.
The reaction temperature is about 0°C to 80°C, preferably
about 0°C to room temperature.
The reaction time is about 2 hours to 48 hours, preferably
about 6 hours to 24 hours.
As an alternative process of Process 2, a phenol or an
alcohol derivative derived from a compound of the formula (9)
(wherein R24 is p-methoxybenzyl and the carboxyl group is
protected by benzyl ester) is subjected to removal of the
p-methoxybenzyl group with 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ), etc., followed by condensation with
a compound of the formula (2) . After removal of the benzyl group
from the resulting compound, the deprotected compound is
condensed with a compound of the formula (8) to give a compound
of the formula (1-2) which is one of the objective compounds.
Process A
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R4 has the same meaning as defined above, R31 is C1-C6
alkyl, and 1' is 1).

In the above reaction scheme, R31 and R4 each has the same
meaning as defined above, R25 is C1-6 alkyl, X2 and X3 each is
halogen, and Et is ethyl.
Step A-l
A compound of the formula (14) can be prepared by reacting
a compound of the formula (12) with a malonic acid ester of
the formula (13) in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; and
polar solvents such as N,N-dimethylformamide, dimethyl
sulfoxide, etc. , and^they can be used solely or in combination
thereof. A preferred solvent in the present reaction is
N,N-dimethylformamide.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ;
alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc.; alkali metal amides
such as sodium amide, lithium bistrimethylsilylamide, etc. ; and
alkali metal carbonates such as sodium carbonate, potassium
carbonate, etc., among which sodium hydride is preferable.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 100°C
The reaction time is about 30 minutes to 24 hours,
preferably about 1 hour to 12 hours.
Step A-2
This step is a hydrolysis reaction of esters, followed
by decarboxylation. A compound of the formula (15) can be
prepared by stirring a compound of the formula (14) under
heating in a solvent in the presence of a base.

The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; alcohols such as methanol,
ethanol, isopropyl alcohol, t-butanol, etc.; and water; and
they can be used solely or in combination thereof. Preferred
solvents in the present reaction are mixtures of an alcohol and
water.
Examples of the bases used in the reaction include alkali
metal carbonates such as sodium carbonate, potassium carbonate,
etc., and alkali metal hydroxides such as lithium hydroxide,
sodium hydroxide, potassium hydroxide, etc. , among which sodium
hydroxide or potassium hydroxide is preferred.
The reaction temperature is about 0°C to 150°C, preferably
about 60°C to 120°C
The reaction time is about 10 minutes to 12 hours,
preferably about 30 minutes to 6 hours.
In accordance with the Steps la-2, la-3 and la-4 of the
Process la, compounds of the present invention can be prepared
from a compound of the formula (15) obtained in the above Step
A-2.
An example in the case where Alk1 is a branched alkanediyl
or alkenediyl will be illustrated below.
Step A-3
A compound of the formula (17) can be prepared by reacting
a compound of the formula (14) with a compound of the formula
(16) in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; and
polar solvents such as N,N-dimethylformamide, dimethyl
sulfoxide, etc. , and they can be used solely or in combination
thereof. Preferred solvents in the present reaction are
N,N-dimethylformamide, etc.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ;
alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc. ; alkali metal carbonates
such as sodium carbonate, potassium carbonate, sodium
bicarbonate, potassium bicarbonate, etc.; alkali metal
hydroxides such as lithium hydroxide, sodium hydroxide,
potassium hydroxide, etc.; alkali metal carboxylates such as
sodium acetate, potassium acetate, etc.; and alkali metal
phosphates such as sodium phosphate, potassium phosphate, etc. ,
among which sodium hydride is preferred.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 100°C
The reaction time is about 10 minutes to 24 hours,
preferably about 30 minutes to 12 hours.
Step A-4
In a similar manner to Step A-2, a compound of the formula
(18) can be prepared from a compound of the formula (17).
In accordance with the Steps la-2, la-3 and la-4 of the
Process la, the compounds of the present invention can be
prepared from a compound of the formula (18) obtained in the
above Step A-4.
Process B
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R3 and R4 each has the same meaning as defined above,
and 1" is 2 or 3).
In the above reaction scheme, R3 and R4 each has the same
meaning as defined above. Me is methyl, and Bn is benzyl.
Step B-l
A compound of the formula ( 20) can be prepared by reacting
a compound of the formula (19) with a brominating agent in a
solvent in the presence of a radical initiator (for example,
2,2'-azobisisobutyronitrile or benzoyl peroxide).
The solvent used in the reaction includes, for example.
hydrocarbons such as benzene, etc., and halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc., and they can be used
solely or in combination thereof. Preferred solvents in the
present reaction are methylene chloride or carbon
tetrachloride.
The brominating agent used in the reaction includes, for
example, bromine, N-bromosuccinimide, etc., among which
N-bromosuccinimide is preferred.
The reaction temperature is about room temperature to
120°C, preferably about 60°C to 100°C
The reaction time is about 10 minutes to 8 hours,
preferably about 30 minutes to 4 hours.
Step B-2
In a similar manner to Step A-l of Process A, a compound
of the formula (22) can be prepared by reacting a compound of
the formula (20) with a compound of the formula (21).
Step B-2'
In a similar manner to Step A-l of Process A, a compound
of the formula (22' ) can be prepared by reacting a compound of
the formula (20' ) (prepared from a compound of the formula (15)
and a compound of the formula (22) via several steps) with a
compound of the formula (21).
Step B-3
A compound of the formula (23) can be prepared by
hydrogenating a compound of the formula (22) for debenzylation
in a solvent, followed by decarboxylation.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dime thoxyethane, diglyme, etc.; alcohols such as methanol,
ethanol, isopropyl alcohol, t-butanol, etc.; and water; and
they can be used solely or in combination thereof. Preferred
solvents in the present reaction are alcohols.
Examples of the catalyst used for the debenzylation
include palladium carbon, palladium hydroxide, Raney-Ni,
platinum oxide, etc., among which palladium carbon is
preferred.
The reaction temperature in the debenzylation is
preferably about room temperature to 80°C, and the reaction
temperature in the dercarboxylation is preferably 10°C to 150°C.
The reaction time in the debenzylation is about 1 hour
to 16 hours, preferably about 2 hours to 8 hours, and the reaction
time in the decarboxylation is about 5 minutes to 4 hours,
preferably about 10 minutes to 2 hours.
Step B-3'
In a similar manner to Step B-3 of Process B, a compound
of the formula (23') can be prepared from a compound of the
formula (22').
In accordance with the Steps 1-3, 1-4 and 1-5 of the
process 1, the compounds of the present invention can be
prepared from a compound of the formula (23) or (23') obtained
in Step B-3 or B-3'.
Process C
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is
(wherein R4 has the same meaning as defined above, R32 is
-CON(R11) (R12) in which R11 and R12 each has the same meaning as
defined above, and 1' is 1).

In the above reaction scheme, R4, R11 and R12 each has the
same meaning as defined above. Me is methyl and t-Bu is
tert-butyl.
Step C-l
An acid chloride can be prepared from a compound of the
formula (24) in a similar manner to Step 1-1 of Process 1. The
resulting acid chloride is reacted with a compound of the
formula (2-5) in a similar manner to Step 1-3 of Process 1 to
give a compound of the formula (25).
Also, a compound of the formula (26) can be prepared by
condensing a compound of the formula (24) with a compound of
the formula (25) using a condensing agent (for example, WSC,
HOBT) . Alternatively, a compound of the formula (24) is
converted into its mixed anhydride, followed by reaction with
a compound of the formula (25) in the presence of a base, to
give a compound of the formula (26).
Step C-2
In a similar manner to Step A-l of Process A, a compound
of the formula (28) *an be prepared by reacting a compound of
the formula (26) with a compound of the formula (27).
Step C-3
A compound of the formula (29) can be prepared by treating
a compound of the formula (28) with an acid (trifluoroacetic
acid, toluenesulfonic acid, methanesulfonic acid, etc. ) in the
presence or absence of a solvent under heating or at room
temperature to convert the tert-butyl ester moiety into the
carboxylic acid moiety, followed by decarboxylation.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.;
halogenated hydrocarbons such as methylene chloride,
chloroform, carbon tetrachloride, 1,2-dichloroethane, etc.;
and water; and they can be used solely or in combination thereof .
Preferred solvents in the present reaction are methylene
chloride, chloroform or toluene.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 100°C
The reaction time is about 1 hour to 24 hours, preferably
about 2 hours to 12 hours.
Step C-4
In a similar manner to Step 1-2 of Process 1, a compound
of the formula (30) can be prepared from a compound of the formula
(29).
In accordance with the Steps 1-3, 1-4 and 1-5 of Process
1, the compounds of the present invention can be prepared from
a compound of the formula (30) obtained in the above Step C-4.
Process D
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R4 has the same meaning as defined above, R33 is C1-6
alkoxy or C7-16 aralkyloxy, and 1' is 1).
sulfoxide, etc. ; and they can be used solely or in combination
thereof. A preferred solvents in the present reaction is
N,N-dimethylformamide.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ,
and alkali metal carbonates such as sodium carbonate, potassium
carbonate, sodium bicarbonate, potassium bicarbonate, etc.,
among which sodium hydride is preferred.
The reaction temperature is about 0°C to 100°C, preferably
about room temperature to 80°C
The reaction tinte is about 2 hour to 48 hours, preferably
about 6 hours to 24 hours.
Step D-2
A compound of the formula (33) can be prepared by
hydrolyzing the ester moiety of a compound of the formula (32)
in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1, 2-dime thoxye thane, diglyme, etc.; alcohols such as methanol,
ethanol, isopropyl alcohol, etc.; and water, and they can be
used solely or in combination thereof. Preferred solvents in
the present reaction are tetrahydrofuran or a mixture of
tetrahydrofuran and ethanol or methanol.
Examples of the bases used in the reaction include alkali
metal carbonates such as sodium carbonate , potassium carbonate ,
etc.; aqueous solutions of alkali metal hydroxides such as
lithium hydroxide , sodium hydroxide , potassium hydroxide , etc.,
among which sodium hydroxide is preferred.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 80°C
The reaction time is about 1 hour to 24 hours, preferably
about 2.5 hours to 12 hours.
Step D-3
In a similar manner to Step 1-1 of Process 1, a compound
of the formula (34 ) can be prepared from a compound of the formula
(33).
Step D-4
This process is a conversion reaction from acid chlorides
to diazoketones . A compound of the formula (35) can be prepared
by reacting a compound of the formula (34) with diazomethane
in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1, 2-dimethoxyethane, diglyme, etc. , and they can be used solely
or in combination thereof. Preferred solvents in the present
reaction are diethyl ether or tetrahydrofuran.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine is
preferred.
The reaction temperature is about -20°C to 50°C,
preferably about 0°C to room temperature.
The reaction time is about 2 hours to 48 hours, preferably
about 6 hours to 2 4 hours.
Step D-5
This process is one carbon homologation (Arndt-Eistert
synthesis) by a-diazoketone rearrangement (Wolff
rearrangement). A compound of the formula (35) is reacted by

use of a silver catalyst (for example, silver benzoate, silver
oxide) in an alcohol in the presence of a base to give a compound
of the formula (36).
The solvent (also served as the reaction reagents) used
in the reaction includes , for example, alcohols such as methanol,
ethanol, isopropyl aicohol, t-butanol, etc., and they can be
used solely or in combination thereof. Preferred solvents
(also served as the reaction reagents) in the present reaction
are methanol or ethanol.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine is
preferred.
The reaction temperature is about room temperature to
120°C, preferably about 60°C to 120°C.
The reaction time is about 2 hours to 36 hours, preferably
about 4 hours to 18 hours.
Step D-6
In a similar manner to Step 1-2 of Process 1, a compound
of the formula ( 37 ) can be prepared from a compound of the formula
(36).
In accordance with the Steps 1-3, 1-4 and 1-5 of the above
Process 1, the compounds of the present invention can be
prepared from a compound of the formula (37) obtained in the
above Step D-6 . The resulting compound of the present invention
is further subjected to the reactions of Step 2-2 of Process
2, whereby the substituent -OR26 can be converted into -OH.
Process E
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R4 has the same meaning as defined above, R34 is
-N(RI3)(R14) in which R13 and R14 each has the same meaning as
defined above), and 1' is 1).
Process E

In the above reaction scheme, R4, R13, R14, Me and t-Bu
each has the same meaning as defined above.
Step E-l
In a similar manner to Step A-l of Process A, a compound
of the formula (39) can be prepared by reacting a compound of
the formula (38) with a compound of the formula (27).
Step E-2
In a similar manner to Step C-3 of Process C, a compound
of the formula ( 40 ) can be prepared from a compound of the formula

(39).
Step E-3
A compound of the formula (42) can be prepared by reacting
a compound of the formula (40) with a compound of the formula
(41) without or in a solvent and in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachlori.de, 1,2-dichloroe thane, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; esters
such as ethyl acetate, methyl acetate, butyl acetate, etc. ; and
polar solvents such as N,N-dimethylformamide, dimethyl
sulfoxide, etc. ; and they can be used solely or in combination
thereof. A preferred solvent in the present reaction is
tetrahydrofuran.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine or a
mixture of triethylamine and dimethylaminopyridine is
preferred.
The reaction temperature is about 0°C to 120°C, preferably
about room temperature to 100°C.
The reiaction time is about 2 hours to 48 hours, preferably
about 6 hours to 24 hours.
Step E-4
In a similar manner to Step 1-2 of Process 1, a compound
of the formula ( 43 ) can be prepared from a compound of the formula
(42).
In accordance with the Steps 1-3, 1-4 and 1-5 of the above
Process 1, the compounds of the present invention can be
prepared from a compound of the formula (43) obtained in the
above Step E-4.
Process F
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R4 has the same meaning as defined above and R35 is
-COO(R25) in which R25 is Ci-Cealkyl, and 1' is 1).
Process F

In the above reaction scheme, R4, R25 and Bn each has the
same meaning as defined above.
Step F-l

In a similar manner to Step 1-1 of Process 1, a compound
of the formula (45 ) can be prepared from a compound of the formula
(44).
Step F-2
A compound of the formula ( 47 ) can be prepared by reacting
a compound of the formula (45) with a compound of the formula
(46) in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, 'hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and esters such as
ethyl acetate, methyl acetate, butyl acetate, etc.; and they
can be used solely or in combination thereof. A preferred
solvent in the present reaction is tetrahydrofuran.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine is
preferred.
The reaction temperature is about -30°C to 80°C,
preferably about -20°C to room temperature.
The reaction time is about 2 hours to 48 hours, preferably
about 6 hours to 24 hours.
Step F-3
In a similar manner to Step A-l of Process A, a compound
of the formula (49) can be prepared by reacting a compound of
the formula (47) with a compound of the formula (48).
Step F-4
A compound of the formula (49) was reacted in a similar
manner to Step 1-2 of Process 1, followed by debenzylation and
decarboxylation to give a compound of the formula (50).
In accordance with the alternative process described in
Step 1-3 and Step 1-5 of Process 1, the compounds of the present
invention can be prepared from a compound of the formula (50)
obtained in the above Step F-4.
Process G
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R3 and R4 each has the same meaning as defined above
and 1' is 1).
of the formula ( 54 ) can be prepared from a compound of the formula
(53).
Step G-4
In a similar manner to Step D-6 of Process D, a compound
of the formula ( 55 ) can be prepared from a compound of the formula
(54).
In accordance with Steps 1-3, 1-4 and 1-5 of the above
Process 1, the compounds of the present invention can be
prepared from a compound of the formula (55) obtained above in
Step G-4.
Step G-5
In a similar manner to Step 1-4 of the above Process 1,
a compound of the formula (55' ) can be prepared from a compound
of the formula (54).
In accordance with Steps la-2, la-3 and la-4 of the above
Process la, the compounds of the present invention can be
prepared from a compound of the formula (55' ) obtained in the
above Step G-5.
Process H
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R3 and R4 each has the same meaning as defined above
and 13 is 0).
In the above reaction scheme, R1, R2, R3, R4, R5, R6, R7,
R8, R9, R23, Alk2, ring A, ring B, ring C, m and n each has the
same meaning as defined above.
Step H-1 .
In a similar manner to Step 1-2 of Process 1, a compound
of the formula ( 57) can be prepared from a compound of the formula
(56).
Step H-2
In a similar manner to Step 1-3 of Process 1, a compound
of the formula (58) can be prepared by reacting a compound of
the formula (57) obtained in Step of H-l (or commercially
available product) with a compound of the formula (3).
Step H-3
In a similar manner to Step 1-4 of Process 1, a compound
of the formula ( 59 ) can be prepared from a compound of the formula
(58).
Step H-4
In a similar manner to Step 1-5 of Process 1, a compound
of the formula (1-3) which is one of the objective compounds
can be prepared by reacting a compound of the formula (59) with
a compound of the formula (8).
Process I
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R3 and R4 each has the same meaning as defined above
and 14 is 1 to 3).
In the above reaction scheme, R1, R2, R3, R4, R5, R6, R7,
R8, R9, 14, m, n, ring A, ring C, Bn, Me, Alk1, Alk2 and X2 each

has the same meaning as defined above.
Step 1-1
In a similar manner to Step 1-3 of Process 1, a compound
of the formula (61) can be prepared by reacting a compound of
the formula (60) with a compound of the formula (3).
Step 1-2
Under conditions similar to Step 1-2 of Process 1, with
the proviso that palladium hydroxide is used as a catalyst, a
compound of the formula (62) can be prepared from a compound
of the formula (61).
Step 1-3
A compound of the formula (64) can be prepared by reacting
a compound of the formula (62) with a compound of the formula
(63) in a solvent in the presence of a base. Alternatively,
X2-(Alk1)14-COOEt (in the formula, X2, Alk1, 14 and Et each has
the same meaning as defined above) may be used in place of a
compound of the formula (63).
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; esters
such as ethyl acetate, methyl acetate, butyl acetate, etc.;
polar solvents such as acetone, N,N-dimethylformamide,
dimethyl sulfoxide, etc.; and they can be used solely or in
combination thereof. A preferred solvent in the present
reaction is N,N-dimethylformamide.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride , etc. ;

alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc.; alkali metal carbonates
such as sodium carbonate, potassium carbonate, etc.; alkali
metal hydroxides such as lithium hydroxide, sodium hydroxide,
potassium hydroxide, etc.; alkali metal carboxylates such as
sodium acetate, potassium acetate, etc.; and alkali metal
phosphates such as sodium phosphate, potassium phosphate, etc. ,
among which potassium carbonate or sodium hydride is preferred.
The reaction temperature is about 0°C to 150°C, preferably
about room temperature to 100°C.
The reaction time is about 1 hour to 48 hours, preferably
about 2 hours to 24 hours.
Step 1-4
In a similar manner to Step 1-4 of Process 1, a compound
of the formula ( 65 ) can be prepared from a compound of the formula
(64).
Step 1-5
In a similar manner to Step 1-5 of Process 1, a compound
of the formula (1-4) which is one of the objective compounds
can be prepared by reacting a compound of the formula (65) with
a compound of the formula (8) .
Process J
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is
(wherein R3, R4 and Alk1 each has the same meaning as defied above
and 14 is 1 to 3).
Process J

In the above reaction scheme, R3, R4, Me, Alk1, 14 and X2
each has the same meaning as defined above.
Step J-1
In a similar manner to Step 1-3 of Process I, a compound
of the formula (67) can be prepared by reacting a compound of
the formula (66) with a compound of the formula (63) .
Alternatively, X2- (Alk1)14-COOEt (in the formula X2, Alk1, 14 and
Et each has the same meaning as defined above) may be used in
place of a compound of the formula (63).
Step J-2
In accordance with the Step 1-4 of Process I, a compound
of the formula (68) can be prepared from a compound of the formula
(67).
In a similar manner to Steps la-2 , la-3 and la-4 of Process
la, the compounds of the present invention can be prepared from
a compound of the formula (68) obtained in the above Step 3-2.
Process K
The following is an example of the process for preparing
a compound of the formula (1) wherein ring B is

(wherein R3, R4, 14 and Alk1 each has the same meaning as defined
above).
Process K

In the above reaction scheme, R3, R4, Me, 14, Alk1 and X2
each has the same meaning as defined above.
Step K-l
In a similar manner to Step 1-3 of Process I, a compound
of the formula (70) can be prepared by reacting a compound of
the formula (69) with a compound of the formula (63).
Alternatively, X2- (Alk1)14-COOEt (in the formula X2, Alk1, 14 and
Et each has the same meaning as defined above) may be used in
place of a compound of the formula (63).
Step K-2
In a similar manner to Step 1-4 of Process I, a compound
of the formula (71) can be prepared from a compound of the formula
(70).
In accordance with the Steps la-2, la-3 and la-4 of the
above Process la, the compounds of the present invention can
be prepared from a compound of the formula (71) obtained in the
above Step K-2.
Process L
The following is an example of the process for preparing
a compound of the formula (1) wherein R3 of the ring B, and R10
of the X are taken together to form

(wherein R4, 14 and Alk1 each has the same meaning as defined
above).
In the above reaction scheme, R1, R2, R4, R5, R6, R7, R8,
R9, 14, m, ring A, ring C, Alk1 and Alk2 each has the same meaning
as defined above.
Step L-l
A compound of the formula (1-5) obtained by debenzylation
of a compound (wherein R26 is benzyl) obtained in the Process
1 and the Process D is reacted with a phosgene equivalent reagent
(for example, triphosgene or diphosgene, etc.) in a solvent in
the presence of a base to give a compound of the formula (1-6) .
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and they can be used
solely or in combination thereof. A preferred solvent in the
present reaction is chloroform.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine is
preferred.
The reaction temperature is about -20°C to 100°C,
preferably about 0°C to room temperature.
The reaction time is about 10 minutes to 4 hours,
preferably about 30 minutes to 2 hours.
Process M
The following is an example of the process for preparing
a compound of the formula (1) wherein R10 is other than hydrogen.
Process M

In the above reaction scheme, R1, R2, R3, R4, R23, 1, n,
X2, ring A, ring B, and Alk1 each has the same meaning as defined
above, and R10 is C1-C6 alkyl or C3-C7 cycloalkyl) .
Step M-l
A compound of the formula ( 73 ) can be prepared by reacting

a compound of the formula (6) obtained in the Step 1-3 of Process
1 with a compound of the formula ( 72) in a solvent in the presence
of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; esters such as ethyl
acetate, methyl acetate, butyl acetate, etc.; and polar
solvents such as acetone, N,N-dimethylformamide, dimethyl
sulfoxide, etc. ; and they can be used solely or in combination
thereof. A preferred solvent in the present reaction is
N,N-dimethylformamide.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ;
alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc.; alkali metal carbonates
such as sodium carbonate, potassium carbonate, etc.; alkali
metal carboxylates such as sodium acetate, potassium acetate,
etc.; and alkali metal phosphates such as sodium phosphate,
potassium phosphate, etc., among which sodium hydride is
preferred.
The reaction temperature is about 0°C to 100°C, preferably
about room temperature to 80°C.
The reaction time is about 1 hour to 24 hours, preferably
about 2 hours to 8 hours.
In accordance with the above Steps 1-4 and 1-5, the
compounds of the present invention can be prepared from a
compound of the formula (73) obtained in the above Step M-l.
Process N
The following is an example of the process for preparing
a compound of the formula (1) wherein R8 and R9 are each
-CONH(R19') (wherein R19' is C1-C6 alkyl) .
Process N

In the above reaction scheme, R5, R6, R7, R25 and ring C
each has the same meaning as defined above.
Step N-l
A compound of the formula (75) can be prepared by reacting
a compound of the formula (74) with thionyl chloride or oxalyl
chloride in a solvent.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and esters such as
ethyl acetate, methyl acetate, butyl acetate, etc.; and they
can be used solely or in combination thereof. A preferred

solvent used in the present reaction is toluene containing a
catalytic amount of N,N-dimethylformamide.
The reaction temperature is about room temperature to
120°C, preferably about 50°C to 100°C.
The reaction time is about 10 minutes to 6 hours,
preferably about 30 minutes to 3 hours.
Step N-2
A compound of the formula (77) can be prepared by reacting
a compound of the formula (75) with a compound of the formula
(76) in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; and esters such as
ethyl acetate, methyl acetate, butyl acetate, etc.; and they
can be used solely or in combination thereof. Preferred
solvents in the present reaction are methylene chloride or
tetrahydrofuran.
Examples of the bases used in the reaction include organic
bases such as triethylamine, pyridine, dimethylaminopyridine,
N-methylmorpholine, etc., among which triethylamine is
preferred.
The reaction temperature is about -40°C to 60°C,
preferably about -30°C to room temperature.
The reaction time is about 2 hours to 48 hours, preferably
about 6 hours to 24 hours.
Step N-3

A compound of the formula ( 78 ) can be prepared by reacting
a compound of the formula (77) with paraformaldehyde or formalin
without or in a solvent in the presence of a catalytic amount
of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; esters
such as ethyl acetate, methyl acetate, butyl acetate, etc. ; and
polar solvents such as N,N-dimethylformamide, dimethyl
sulfoxide, etc. ; and they can be used solely or in combination
thereof. A preferred solvent in the present reaction is
tetrahydrofuran.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ;
alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc.; alkali metal hydroxides
such as sodium hydroxide, potassium hydroxide, lithium
hydroxide, etc.; alkali metal carbonates such as sodium
carbonate, potassium carbonate, etc.; and organic bases such
as triethylamine, diethylamine, pyridine, etc., among which
potassium t-butoxide, sodium ethoxide or potassium hydroxide
is preferred.
The reaction temperature is about 0°C to 100°C, preferably
about room temperature to 80°C.
The reaction time is about 10 minutes to 24 hours,
preferably about 30 minutes to 12 hours.
In accordance with the above Processes 1, la and 2, the
compounds of the present invention can be prepared using a
compound of the formula (78) obtained in the above Step N-3 in
place of a compound of the formula (8).
Process O
The following is an example of the process for preparing
a compound of the formula (1) wherein R8 and R9 are each -COOR25
(wherein R25 is C1-C6 alkyl) .
Process 0

In the above reaction scheme, R5, R6, R7, R25 and ring C
each has the same meaning as defined above.
Step 0-1
In a similar manner to Step N-3 of Process N, a compound
of the formula ( 80 ) can be prepared from a compound of the formula
(79).
In accordance with the above Processes 1, la and 2, the
compounds of the present invention can be prepared using a
compound of the formula (80) obtained in the above Step 0-1 in
place of a compound of the formula (8).
Process P
The following is an example of the process for preparing
a compound of the formula (1) wherein m is 2 or 3. In this
process, tert-butyldimethylsilyl (TBS) may be used in place of
benzyl (Bn).
Process P

In the above reaction scheme, R5, R6, R7, R8, R9, X2, m,
Bn and ring C each has the same meaning as defined above.
Step P-1
A compound of the formula (83) can be prepared by reacting
a compound of the formula (81) with a compound of the formula
(82) in a solvent in the presence of a base.
The solvent used in the reaction includes, for example,
ethers such as diethyl ether, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as
benzene, toluene, hexane, xylene, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform, carbon
tetrachloride, 1,2-dichloroethane, etc.; alcohols such as
methanol, ethanol, isopropyl alcohol, t-butanol, etc.; esters
such as ethyl acetate, methyl acetate, butyl acetate, etc. ; and
polar solvents such as N,N-dimethylformamide, dimethyl
sulfoxide, etc. ; and they can be used solely or in combination
thereof. Preferred solvents in the present reaction are
N,N-dimethylformamide or tetrahydrofuran.
Examples of the bases used in the reaction include alkali
metal hydrides such as sodium hydride, potassium hydride, etc. ;
alkali metal alkoxides such as sodium ethoxide, sodium
methoxide, potassium t-butoxide, etc. ; alkali metal carbonates
such as sodium carbonate, potassium carbonate, etc.; and
organoalkali metals such as lithium diisopropylamide, etc.,
among which sodium hydride or lithium diisopropylamide is
preferred.
The reaction temperature is about 0°C to 100°C, preferably
about room temperature to 80°C
The reaction time is about 30 minutes to 48 hours,
preferably about 2 hours to 24 hours.
Step P-2
In a similar manner to Step 2-2 of Process 2, a compound
of the formula ( 84 ) can be prepared from a compound of the formula
(83).
In accordance with the above Processes 1, la and 2, the
compounds of the present invention can be prepared using a
compound of the formula (84) obtained in the above Step P-2 in
place of a compound of the formula (8).
Examples
The present invention is illustrated in more detail by
Examples given below, but it goes without saying that the
present invention is not limited thereto. In the Examples, Me
is methyl, Et is ethyl, tBu is t-butyl and TBS is
tert-butylmethylsilyl.
Example 1
4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]phenyl-
acetic acid. 2,2-bisethylcarbamoyl-2-phenylethyl ester
a) phenylmalonic acid dichloride

Thionyl chloride (13 . 7 mL) was added dropwise to a mixture
of phenylmalonic acid (11.31 g), dimethylformamide (230 mL)
and toluene (27 mL) under ice-cooling. The mixture was
stirred at 80°C for 70 minutes, and the solvent was removed
off by evaporation. After azeotropic distillation with
toluene, the residue was dried in vacuo to give the title
compound (11.61 g) .
b) Phenylmalonic acid diethylamide

To a mixed solution of ethylamine in tetrahydrof uran (2M,
45.5 mL), triethylamine (13.9 mL) and methylene chloride (80
mL) was dropwise added the phenylmalonic acid dichloride (8.99
g) obtained in Example 1-a) at -20°C. The mixture was stirred
overnight while the temperature was raised to room temperature,
and then diluted with ethyl acetate after addition of 3N
hydrochloric acid. The organic layer was washed with
saturated brine, saturated aqueous sodium bicarbonate and
saturated brine, dried over sodium sulfate and concentrated.
The resulting solid was washed with ethyl acetate and hexane
to give the title compound (4.85 g) as a white powder,
c) 2-Hydroxymethyl-2-phenylmalonic acid diethylamide

The phenylmalonic acid diethylamide (2.34 g) obtained in
Example 1-b) and paraformamide (390 mg) were suspended in
tetrahydrofuran (20 ml), and to this suspension was added
potassium hydroxide (catalytic amount) at 60°C. The mixture
was stirred for 5 hours and concentrated to remove the solvent.
The residue was chromatographed on a column of silica gel with
ethyl acetate:hexane=l:1 to give the title compound (2.31 g).
d) 4'-Trifluoromethylbiphenyl-2-carboxylic acid chloride

To a mixture of 4'-trifluoromethylbiphenyl-2-carboxylic
acid (5.06 g), dimethylformamide (catalytic amount) and
methylene chloride (30 mL) was added dropwise oxalyl chloride
(2.43 mL) under ice-cooling. The mixture was stirred at room
temperatures for 100 minutes and the solvent was removed by
evaporation. After azeotropic distillation with toluene, the
residue was dried in vacuo to give the title compound (5.40 g) .
e) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]phenyl-
acetic acid, ethyl ester

To a mixture of 4-aminophenylacetic acid ethyl ester
(3.41 g) , triethylamine (3.2 mL) and methylene chloride (30 mL)
was added dropwise a solution of the 4' -
trifluoromethylbiphenyl-2-carboxylic acid chloride (5.40 g)
obtained in Example 1-d) in methylene chloride (10 mL) under
ice-cooling, and the mixture was stirred, at room temperature
overnight. After addition of IN hydrochloric acid, the
reaction mixture was diluted with ethyl acetate, and the organic
layer was washed with saturated brine, saturated aqueous sodium
bicarbonate and saturated brine, dried over sodium sulfate, and
then concentrated to give the title compound (8.12 g).
f) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)aminoJphenyl-
acetic acid

The 4-[(4'-Trifluoromethylbiphenyl-2-
carbonyl)amino]phenylacetic acid ethyl ester (8.12 g) obtained
in Example 1-e) was dissolved in 40 mL of tetrahydrofuran and
20 mL of ethanol. After addition of 4N sodium hydroxide (5 mL) ,
the solution was stirred at room temperature for 5 hours and
concentrated. The powder formed upon addition of 1N
hydrochloric acid was collected by filtration and dried in vacuo
to give the title compound (7.48 g).
g) 4- [(4 ' -Trifluoromethylbiphenyl-2-carbonyl)amino]phenyl-
acetic acid 2,2-bisethylcarbamoyl-2-phenylethyl ester

The 4- [(4'-Trifluoromethylbiphenyl-2-
carbonyl)amino]phenylacetic acid (519 mg) obtained in Example
1-f), the 2-hydroxymethyl-2-phenylmalonic aid 'diethylamide
(317 mg) obtained in Example 1-c), dimethylaminopyridine (171
mg) and 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride (WSC.HC1)(268 mg) were dissolved in methylene
chloride (5 ml) . The solution was stirred at room temperature
for 6 hours and the solvent was removed off by evaporation. The
residue was purified by column chromatography on silica gel with
ethyl acetate :hexane=l: 1 to 3:2 to give the title compound (725
mg)(see Table 1).
Example 1-2
2-Phenyl-2-{2-[4-(4'-trifluoromethylbiphenyl- 2 -
carbonyloxy)phenyl]acetoxymethyl}malonic acid diethyl ester
a) 2-Hydroxymethyl-2-phenylmalonic acid diethyl ester

Paraformaldehyde (720 mg) was suspended in phenylmalonic
acid diethyl ester (4.73 g), and a catalytic amount of potassium
hydroxide was added thereto at 60°C. After stirring for 1.5
hours, the reactidn mixture was purified by column
chromatography on silica gel with ethyl acetate:hexane=l:5 to
1:2 to give the title compound (4.96 g).
b) 2-[2-(4--(Benzyloxyphenyl)acetoxymethyl] -2-phenylmalonic
acid diethyl ester

4-Benzyloxyphenylacetic acid (1.09 g) was suspended in
methylene chloride (50 mL) and the suspension was dissolved by
addition of dimethylaminopyridine (0.511 g). To the solution
was added the 2-hydroxymethyl-2-phenylmalonic acid diethyl
ester (1.20 g) obtained in Example 1-2 a), and
1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide
hydrochloride (0.864 g) was portionwise added thereto. The
mixture was stirred at room temperature overnight and then
concentrated. The residue was purified by column
chromatography on silica gel with ethyl acetate:hexane=l:4 to
give the title compound (1.95 g) as a colorless oil.
c) 2-[2-(4-(Hydroxyphenyl)acetoxymethyl]- 2 -phenylmalonic
acid diethyl ester

The 2-[2-(4-(Benzyloxyphenyl)acetoxymethyl]-2-phenyl-
malonic acid diethyl ester (1.95 g) obtained in Example 1-2 b)
was dissolved in methanol (2.5 mL) . The solution was subjected
to hydrogenation in the presence of 7.5% palladium-carbon
(0.200 g) under normal pressure for 4 hours. The reaction
solution was filtered through a Celite pad and concentrated to
give the title compound (1.71 g) as a colorless oil.
d) 2-Pheny1-2-{2-[4-(4'-trifluoromethylbiphenyl-2-
carbonyloxy)phenyl]acetoxymethyl}malonic acid diethyl ester

4'-Trifluoromethylbiphenyl-2-carboxylic acid (0.266 g)
was suspended in methylene chloride (10 mL), and the suspension
was dissolved by addition of 4-dimethylaminopyridine (0.122 g) .
To the solution was added the
2-[2-(4-(hydroxyphenyl)acetoxymethyl]-2-phenylmalonic acid
diethyl ester (0.400 g) obtained in Example 1-2 c), and
1-ethyl-3-(3'- dimethylaminopropyl)carbodiimide
hydrochloride (0.192 g) was portionwise added thereto. The
mixture was stirred at room temperature overnight and then
concentrated. The residue was purified by column
chromatography on silica gel with ethyl acetate :hexane=l: 3 to
give the title compound (0.55 g) as an
amorphous powder (see Table 1).
Example 1-3
2-(2-{3-Methyl-4-[(4'-trifluoromethylbiphenyl- 2 -
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester
a) 2-(3-Methyl-4-nitrophenyl)malonic acid diethyl ester

Sodium hydride (60% mineral oil; 0.599 g) was suspended
in dimethylformamide (10 mL), and a solution of malonic acid
diethyl ester (2.00 g) in dimethylf ormamide (10 mL) was added
dropwise thereto under ice-cooling. After foam generation is
stopped, a solution of 4-fluoro-2-methylnitrobenzene (1.94 g)
in dimethylf ormamide ( 5 mL) was added thereto, and the reaction
temperature was raised to 100°C, followed by stirring for 6 hours .
The reaction mixture was concentrated, acidified with 1N
hydrochloric acid and extracted with ethyl acetate. The
extract was washed successively with water and saturated brine,
dried over sodium sulfate and concentrated. The residue was
purified by column chromatography on silica gel with ethyl
acetate:hexane=l:5 to give the title compound (1.65 g) as a
yellow oil.
b) (3-Methyl-4-nitrophenyl)acetic acid-"

Potassium hydroxide (0.168 g) was dissolved in 7 mL of
methanol and 1 mL of water, and the 2- (3-methyl-4-
nitrophenyl)malonic acid diethyl ester (0.250 g) obtained in
Example 1-3 a) was dissolved in the solution. The solution was
stirred at 100°C for 2 hours and concentrated. The residue was
acidified with 2N hydrochloric acid and extracted with ethyl
acetate. The extract was washed with saturated brine, dried
over sodium sulfate and concentrated to give the title compound
(0.143 g) as a yellow solid.
c) 2-[2-(3-Methyl-4-nitrophenyl)acetoxymethyl]-2-phenyl-
malonic acid diethyl ester

The (3-Methyl-4-nitrophenyl)acetic acid (0.143 g)
obtained in Example 1-3 b) was dissolved in methylene chloride
(5 mL). To the solution were added
2-(3-methyl- 4-nitrophenyl)malonic acid diethyl ester (0.195
g) obtained in Example 1-2 a), 4-dimethylaminopyridine (0.090
g) and 1-ethyl-3-(3'- dimethylaminopropyl)carbodiimide
hydrochloride (0.141 g), and the mixture was stirred at room
temperature overnight. The reaction mixture was concentrated
and the residue was purified by column chromatography on silica
gel with ethyl acetate:hexane=l:4 to give the title compound
(0.219 g) as a yellow oil.
d) 2-[2-(4-Amino-3-methylphenyl)acetoxymethyl]-2-phenyl-
malonic acid diethyl ester

The 2-[2-(3-Methyl-4-nitrophenyl}acetoxymethyl]-2-
phenyl-malonic acid diethyl ester (0.219 g) obtained in Example
1-3 c) was dissolved in methanol (3 mL). The solution was
subjected to hydrogenation in the presence of 7.5%
palladium-carbon (0.030 g) under normal pressure to give the
title compound (0.197 g) as a yellow oil.
e) 2-(2-{3-Methyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester
In a similar manner to Example 1 d), 4'-trifluoro-
methyl-2-biphenylcarboxylic acid (0.124 g) was converted into
its corresponding acid chloride. On the other hand, the title
compound (0.215 g) was obtained as a colorless amorphous from
the 2-[2-(4-amino-3-methylphenyl)acetoxymethyl]-2-
phenylmalonic acid diethyl ester (0.197 g) obtained in Example
1-3 d) in a similar manner to Example 1 e)(see Table 1).
Example 1-4
2-(2 -{4-[Methyl-(4'-trifluoromethylbipheny1- 2 -
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester
a) {4-[Methyl-(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid ethyl ester

Sodium hydride (51 mg) was dissolved in dimethylf ormamide
(5 mL) , and the solution was cooled to 0°C. To the solution
was added the 4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenylacetic acid ethyl ester (500 mg)
obtained in Example 1 e), and the mixture was stirred for one
hour. After addition of iodomethane (183 mg) , the mixture was
stirred at room temperature for 3 hours and water was then added.
The reaction solution was concentrated, diluted with ethyl
acetate, and washed with water. The resulting solution was
dried over sodium sulfate and purified by column chromatography
on silica gel with hexane:ethyl acetate=4:l to give the title
compound (141 mg).
b) 2-(2-{4-[Methyl-(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyi}acetoxymethyl)-2-phenylmalonic acid
diethyl ester

The {4 -[Methyl-(4'-trifluoromethylbiphenyl-2 -
carbonyl)amino]phenyl}acetic acid ethyl ester (141 mg)
obtained in Example 1-4 a) was subjected to reactions similar
to those in Examples 1 f) and 1 g) to give the title compound
(56 mg)(see Table 1).
Example 1-5
{3-Ethyl-4-[(4'-trifluoromethylbiphenyl-2 -
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-
2-phenylethyl ester
a) . 3-Ethyl-4-nitrophenylacetic acid ethyl ester
To a solution of 4-nitrophenylacetic acid ethyl ester
(1. 63 g) in tetrahydrofuran (100 mL) was dropwise added 2M ethyl
magnesium chloride in tetrahydrofuran (3 mL) at -15°C under
argon atmosphere, and the mixture was stirred at the same
temperature for 30 minutes. After further dropwise addition
of 2M ethyl magnesium chloride in tetrahydrofuran (3 mL), the
mixture was stirred at -15°C for one hour, and 2 , 3-dichloro-5 , 6-
dicyano-1,4-benzoquinone (3.0 g) was added thereto at the same
temperature. The mixture was stirred overnight, and water (300
mL) was added thereto, followed by extraction with chloroform
(150 mL x 3). The organic layers were combined, washed with
saturated brine, dried over sodium sulfate and purified by
column chromatography on silica gel with hexane:ethyl
acetate=10:l to give the title compound (1.09 g) .
b) {3-Ethyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-
2-phenylethyl ester

The 3-ethyl-4-nitrophenylacetic acid ethyl ester (1.05
g) obtained in Example 1-5 a) was subjected to reactions similar
to those in Example 1-3 d) , Example 1 e) , Example 1 f) and Example
1 g) to give the title compound (1.60 g)(see Table 1).
Examples 1-6 to 1-83
Compounds of Examples 1-6 to 1-85 were obtained in a similar
manner to Examples 1 to 1-5. The compounds obtained were shown
in Tables 2 to 17.
Example 2
{3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester
a) 5-Chloro-N,N-dimethyl-2-nitrobenzamide

The acid chloride obtained from 5-chloro-2-nitrobenzoic
acid (5.0 g) in a similar manner to Example 1 d) was subjected
to reactions similar to those in Example 1 e) to give the title
compound (5.5 g).
b) 2-(3-Dimethylcarbamoyl-4-nitrophenyl)malonic acid
tert-butyl ester methyl ester

Sodium hydride (350 mg) was dissolved in
dimethylformamide (10 mL) , and the solution was cooled to 0°C.
After addition of tert-butyl methyl malonate (1.52 g) , the
mixture was stirred for one hour, and the 5-chloro-N, N-
dimethyl-2 -nitrobenzamide (1.0 g) obtained in Example 2 a) was
added thereto. The mixture was stirred at 70°C for 4 .5 hours
and water was added thereto. The resulting solution was
concentrated, diluted with ethyl acetate and washed with water.
The organic layer was dried over sodium sulfate and purified
by column chromatography on silica gel with ethyl
acetate:hexane=l:1 to give the title compound (1.29 g).
c) (3-Dimethylcarbamoyl-4-nitrophenyl)acetic acid methyl
ester

The 2-(3-dimethylcarbamoyl-4-nitrophenyl)malonic acid
tert-butyl ester methyl ester (1.22 g) obtained in Example 2
b) was dissolved in dichloromethane (10 mL), and the solution
was cooled to 0°C. After addition of trifluoroacetic acid (10
mL) , the mixture was stirred at room temperature for 6 hours,
and concentrated, followed by azeotropic distillation with
toluene. The residue was purified by column chromatography
on silica gel with ethyl acetate :hexane=3:1 to give the title
compound (712 mg).
d) (4-Amino-3-dimethylcarbamoylphenyl)acetic acid methyl
ester

The (3-dimethylcarbamoyl-4-nitrophenyl)acetic acid
methyl ester (683 mg) obtained in Example 2 c) was subjected
to reactions similar to those in Example 1-3 d) to give the title
compound (627 mg).
e) {3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-
2-carbonyl)amino]phenyl}acetic acid
The (4-amino-3-dimethylcarbamoylphenyl)acetic acid
methyl ester (627 mg) obtained in Example 2 d) was subjected
to reactions similar to those in Example 1 e) and Example 1 f)
to give the title compound (1.07 g)(see Table 65).
f) {3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester

The {3-Dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)amino]phenyl}acetic acid (517 mg)
obtained in Example 2 e) was subjected to reactions similar to
those in Example 1 g) to give the title compound (387 mg)(see
Table 18).
Examples 2-2 to 2-119
Compounds of Examples 2-2 to 2-119 were obtained in a
similar manner to Example 2. The compounds thus obtained were
shown in Tables 18 to 41. In addition, compound of Example 2-17
e) was obtained in a similar manner to Example 2 e) and the
compounds thus obtained were shown in Table 65.
Example 3
2-(2-{3-Ethoxy-4 -[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester
5
a) 3-Ethoxy-4-nitrobenzoic acid methyl ester

To a suspension of sodium hydride (60% mineral oil: 1.20g)
in dimethylformamide (50 mL) was added 3-hydroxy-4-
10 nitrobenzoic acid methyl ester (4.93 g) under ice-cooling, and
the mixtures was stirred at room temperature for 30 minutes.
After addition of ethyl iodide (4.4 g) , the solution was stirred
at 60°C overnight, cooled down to room temperature, poured into
saturated aqueous ammonium chloride, and extracted with ethyl
15 acetate-tetrahydrofuran. The organic layer was washed with
saturated aqueous ammonium chloride and saturated brine, dried
over sodium sulfate and concentrated to give a solid, which was
washed with ethyl acetate-hexane to afford
3-ethoxy-4-nitrobenzoic acid methyl ester (3.30 g) as a pale
20 yellow solid.
b) 3-Ethoxy-4-nitrobenzoic acid chloride

3-Ethoxy-4-nitrobenzoic acid chloride was obtained in a
similar manner to Example 1 f) and Example 1 d) from the
3-ethoxy-4-nitrobenzoic acid methyl ester obtained in Example
3 a) .
c) 2'-Diazo-3-ethoxy-4-nitroacetophenone

A solution of the 3-ethoxy-4-nitrobenzoic acid chloride
(2.06 g) obtained in Example 3 b) in diethyl ether (30 mL) was
added dropwise to a mixture of diazomethane in diethyl ether
(0.35M, 64 mL) and triethylamine (3.12 mL) under ice-cooling.
The mixture was stirred for 2 hours under ice-cooling and the
temperature was raised to room temperature, followed by
stirring overnight. After addition of acetic acid (1 mL) , the
mixture was stirred at room temperature for one hour and
evaporated to remove the solvent. The residue was purified by
column chromatography on silica gel with hexane:ethyl
acetate=5:2 to give the title compound (1.80 g) as a yellow
solid.
d) 3-Ethoxy-4-nitrophenylacetic acid ethyl ester

A solution of silver benzoate (270 mg) in triethylamine
(2.7 ml) was added dropwise in 10 divided doses to a solution
of the 2'-diazo-3-ethoxy-4-nitroacetophenone (1.80 g)
obtained in Example 3 c) in ethanol (25 mL) under reflux. The
mixture was refluxed for 9 hours and the reaction solution was
filtered through a Celite pad. The filtrate was concentrated,
and the concentrate was diluted with diethyl ether and washed
with 10% aqueous sodium carbonate, water and saturated brine.
The organic layer was dried over sodium sulfate and purified
by column chromatography on silica gel with hexane:ethyl
acetate=4:l to give the title compound (1.27 g) as a yellow
solid.
e) 4-Amino-3-ethoxyphenylacetic acid ethyl ester

The 3-ethoxy-4-nitroacetic acid methyl ester (1.27 g)
obtained in Example 3 d) was subjected to reactions similar to
those in Example 1-3 d) to give the title compound (1.12 g) as
a brown oil.
f) 2-(2-{3~Ethoxy-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester

The 4-amino-3-ethoxyphenylacetic acid ethyl ester
obtained in Example 3 e) and the 2-hydroxymethyl-2-
phenylmalonic acid diethyl ester obtained in Example 1-2 a) were
subjected to reactions similar to those in Examples 1 e), 1 f)
and 1 g) to give the title compound (0.159 g) (see Table 42).
Example 3-2
{3-Hydroxy-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester

{3-Benzyloxy-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-
2-phenylethyl ester (300 mg) obtained in a similar manner to
Example 3, except that reduction of the nitro group was carried
out with iron dust, was subjected to reactions in a similar
manner to Example 1-2 c) to give the title compound (244 mg)(See
Table 42).
Examples 3-3 to 3-16
Compounds of Examples 3-3 to 3-16 were obtained in a
similar manner to Examples 3 to 3-2. The compounds thus
obtained were shown in Tables 42 to 45.
Example 4
2-{3-Dimethylamino-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester
a) 2-(3-Bromo-4-nitrophenyl)malonic acid tert-butyl ester
methyl ester

Sodium hydride (60%, mineral oil; 0.985 g) was suspended
in dimethylformamide (20 mL) , and a solution of tert-butyl
methyl malonate (4.29 g) in dimethylf ormamide (5 mL) was added
dropwise thereto under ice-cooling. After foam generation is
stopped, a solution of 2-bromo-4-fluoro-1-nitrobenzene (2.71
g) in dimethylformamide (5 mL) was added dropwise thereto at
the same temperature, and the mixture was further stirred at
60°C for 3 hours, and then concentrated. The residue was
neutralized with 1N hydrochloric acid and extracted with ethyl
acetate. The extract was washed with saturated brine, dried
over sodium sulfate and concentrated. The residue was purified
by column chromatography on silica gel with ethyl
acetate:hexane=l:4 to 1:5 to give the title compound (7.54 g)
as an oil.
b) (3-Bromo-4-nitrophenyl)acetic acid methyl ester

The 2-(3-bromo-4-nitrophenyl)malonic acid tert-butyl
ester methyl ester (1.18 g) obtained in Example 4 a) was
dissolved in chloroform (10 mL), trifluoroacetic acid (10 g)
was added thereto under ice-cooling, and the mixture was stirred
at room temperature for 5 hours. The reaction mixture was
poured gradually into ice and saturated aqueous sodium
bicarbonate, and extracted with ethyl acetate. The extract was
washed with water and saturated brine, dried over sodium sulfate
and concentrated to give the title compound (0.820 g) as a pale
yellow oil.
c) (3-Dimethylamino-4-nitrophenyl)acetic acid methyl ester

The (3-bromo-4-nitrophenyl)acetic acid methyl ester
(0.320 g) obtained in Example 4 b) was dissolved in
tetrahydrofuran (10 mL). To this solution were added
triethylamine (0.237 g) and dimethylamine (2M tetrahydrofuran ;
0.58 mL), and stirred overnight while heating. The reaction
mixture was concentrated and purified by column chromatography
on silica gel with ethyl acetate: hexane=l: 4 to give the title
compound (0.145 g) as an orange oil.
d) (4-Amino-3-dimethylaminophenyl)acetic acid methyl ester

The (3-dimethylamino-4-nitrophenyl)acetic acid methyl
ester (0.245 g) obtained in Example 4 c) was subjected to
reactions similar to those in Example 1-3 d) to give the title
compound (0.188 g) as a red oil.
e) 2-{3-Dimethylamino-4-[(4'-trifluoromethylbiphenyl-
2-carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester

The (4-amino-3-dimethylaminophenyl)acetic acid methyl
ester (0.188 g) obtained in Example 4 d) was subjected to
reactions similar to those in Example 1 e), 1f) and 1 g) to
give the title compound (0.058 g) (See Table 46).
Examples 4-2 to 4-8
Compounds of Examples 4-2 to 4-8 were obtained in a similar
manner to Example 4. The compounds thus obtained were shown
in Tables 46 to 47.
Example 5
2-[2-(2-{2-methyl-3-[(4'-trifluoromethylbiphenyl- 2 -
carbonyl)am;Lno]phenyl}acetoxy)ethyl] -2-phenylmalonic acid
diethyl ester
a) 2'-Diazo-3-nitro-2-methylacetophenone

2-Methyl-3-nitrobenzoic acid (500 mg) was subjected to
reactions similar to those in Example 3 b) and 3 c) to give the
title compound (377 mg).
b) 2-Methyl-3-nitrophenylacetic acid ethyl ester

The 2'-diazo-3-nitro-2-methylacetophenone (377 mg)
obtained in Example 5 a) was subjected to reactions similar to
those in Example 3 d) to give the title compound (363 mg).
c) 2-Methyl-3-nitrophenylacetic acid

The 2-methyl-3-nitrophenylacetic acid ethyl ester (352
mg) obtained in Example 5 b) was subjected to reactions similar
to those in Example 1 f) to give the title compound (307 mg) .
d) 2-(2-Benzyloxyethyl)-2-phenylmalonic acid diethyl ester
Sodium hydride (406 mg) was dissolved in
dimethylformamide (20 mL) and the solution was cooled to 0°C.
To this solution was added phenylmalonic acid diethyl ester
(2.0 g), and the mixture was stirred at room temperature for
30 minutes. Bromoethyl benzyl ether (2.0 g) was further added
thereto, stirred at 60°C for 4 hours, and water was added
thereto. The reaction mixture was concentrated, diluted with
ethyl acetate, washed with water, dried over sodium sulfate
and purified by column chromatography on silica gel with ethyl
acetate:hexane=l:9 to give the title compound (1.2 g).
e) 2-(2-Hydroxyethyl)-2-phenylmalonic acid diethyl ester

The 2-(2-benzyloxyethyl)-2-phenylmalonic acid diethyl
ester (1.2 g, not purified) obtained in Example 5 d) was
subjected to reactions similar to those in Example 1-2 c) to
give the title compound (726 mg).
f ) 2-{2-[2-(2-Methyl-3-nitrophenyl)acetoxy]ethyl}-2-
phenylmalonic acid diethyl ester
The 2-methyl-3-nitrophenylacetic acid (307 mg) obtained
in Example 5 c), 4-dimethylaminopyridine (217 mg) and the
2-(2-hydroxyethyl)-2-phenylmalonic acid diethyl ester (250
mg) obtained in Example 5 e) were subjected to reactions similar
to those in Example 1-3 c) to give the title compound (366 mg) .
g) 2-[2-(2-{2-methyl-3-[(4'-trifluoromethylbiphenyl- 2 -
carbonyl)amino]phenyl}acetoxy)ethyl]-2-phenylmalonic acid
diethyl ester

The 2-{2-[2-(2-methyl-3-nitrophenyl)acetoxy]ethyl}-2-
phenylmalonic acid diethyl ester (34 5 mg) obtained in Example
5 f) was subjected to reactions similar to those in Example 1-3
d) and 1-3 e) to give the title compound (318 mg) (See Table 48) .
Examples 5-2 to 5-18
Compounds of Examples 5-2 to 5-18 were obtained in a
similar manner to Example 5. The compounds thus obtained were
shown in Tables 4 8 to 51.
Example 6
4- [ ( 4'-Trifluoromethylbiphenyl-2-carbonyl)amino]benzoic
acid 2-[9-(2,2,2-trifluoroethylcarbamoyl)-9H-fluoren-
9-yl]ethyl ester
a) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]benzoic
acid ethyl ester

4-Aminobenzoic acid ethyl ester (0.568 g) and
triethylamine (0.570 g) were dissolved in methylene chloride
(20 mL), and to this solution was dropwise added a solution of
4'-trifluoromethylbiphenyl-2-carboxylic acid chloride, which
is prepared from 4 ' -trif luoromethylbiphenyl-2-carboxylic acid
(1.00 g) in a similar manner to Example 1 d), in methylene
chloride under ice-cooling. The solution was stirred at room
temperature for 2 hours, followed by addition of methylene
chloride (100 mL). The reaction mixture was washed with 2N
hydrochloric acid and saturated brine, dried over sodium
sulfate and concentrated to give the title compound (1.43 g).
b) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]benzoic
acid

The 4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]benzole acid ethyl ester (0.700 g) obtained in
Example 6 a) was subjected to reactions similar to Example 1
f) to give the title compound (0.680 g) as a white solid,
c) 9-[2-(Tert-butyldimethylsilanyloxy)ethyl]-9H-fluoren-
9-carboxylic acid (2,2,2-trifluoroethyl)amide

9H-Fluorene-9-carboxylic acid (2,2,2-
trifluoroethyl)amide (3.00 g) was dissolved in tetrahydrofuran
(100 mL) , and to this solution was added dropwise a 1. 5M solution
(13.7 mL) of lithium diisopropylamide under ice-cooling. The
mixture was stirred for one hour under ice-cooling, and to this
was added a solution of tert-butyldimethylsilanyloxyethyl
bromide (2.46 g) in tetrahydrofuran (5 mL). The temperature
was gradually raised from under ice-cooling to room temperature,
and the mixture was stirred overnight. Saturated aqueous
ammonium chloride was added to the reaction mixture under
ice-cooling and then extracted with ethyl acetate (50 mL x 2) .
The extract was washed with saturated brine, dried over sodium
sulfate and purified by column chromatography on silica gel with
ethyl acetate :hexane = l: 2 . 5 to give the title compound (6.00 g) .
d) 9-(2-Hydroxyethyl)-9H-fluoren-9-carboxylic acid
(2,2,2-trifluoroethyl)amide
The 9 -[2-(Tert-butyldimethylsilanyloxy)ethyl] -9H-
fluoren-9-carboxylic acid (2,2,2-trifluoroethyl)amide (6.00
g) obtained in Example 6 c) was dissolved in tetrahydrofuran
(13 mL) - acetic acid (39 mL) - water (13 mL). The solution
was stirred at room temperature for 20 hours and concentrated
in vacuo. The residue was purified by column chromatography
on silica gel with ethyl acetate:hexane=l: 1 to give the title
compound (3.80 g).
e) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]benzoic
acid 2-[9-(2,2,2-trifluoromethylcarbamoyl)-9H-fluoren-9-
yl]ethyl ester
The 4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]benzole acid (0.345 g) obtained in Example 6 b)
and the 9-(2-hydroxyethyl)-9H-fluoren-9-carboxylic acid
(2, 2, 2-trifluoroethyl)amide (0.300 g) obtained in Example 6 d)
were subjected to reactions similar to those in Example 1 g)
to give
the title compound (0.390 g) as a colorless solid (see Table
52) .
Examples 6-2 to 6-22
Compounds of Examples 6-2 to 6-22 were obtained in a
similar manner to Examples 6, 1-2 b), 1-2 c) and 1-2 d). The
compounds thus obtained were shown in Tables 52 to 56.
Example 7
Trans-4-[(4'-1rifluoromethylbiphenyl- 2 -
carbonyl) ami.no ]cyclohexanecarboxylic acid 2-[9-(2,2,2-
trifluoroethylcarbamoyl)-9H-fluoren-9-yl]ethyl ester
a) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]cyclo-
hexanecarboxylic acid

4-Amino-cyclohexanecarboxylic acid (0.538 g) was
dissolved in 4N sodium hydroxide (0.933 mL), and to this
solution were dropwise added simultaneously a solution of the
acid chloride which is obtained from
4'-trifluoromethylbiphenyl-2-carboxylic acid (1.0 g) in a
similar manner to Example 1 d) in tetrahydrofuran (5 mL) and
4N aqueous sodium hydroxide (0.933 mL) under ice-cooling. The
mixture was stirred at room temperature for one hour, acidified
with 2N hydrochloric acid and extracted with ethyl acetate . The
extract was washed with saturated brine and dried over sodium
sulfate to give the title compound (1.20 g) as a colorless
powdery solid.
b) Trans-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]cyclohexanecarboxylic acid 2-[9-(2,2,2-
trifluoroethylcarbamoyl)-9H-fluoren-9-yl]ethyl ester
The 4 -[(4'-trifluoromethylbiphenyl- 2 -
carbonyl)amino]cyclohexanecarboxylic acid (0.570 g) obtained
in Example 7 a) and 9-(2-hydroxyethyl)-9H-fluoren-9-
carboxylic acid (2,2,2-trifluoroethyl)amide (0.500 g)
obtained in Example 6 d) were treated in a similar manner to
Example 1 g) to give the title compound (0.534 g) as a colorless
solid (see Table 57).
Examples 7-2 to 7-5
Compounds of Examples of 7-2 to 7-5 were obtained in a
similar manner to Example 7. The compounds thus obtained were
shown in Table 57.
Example 8
2-Phenyl-2-(2-{4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]piperidin-1-yl}acetoxymethyl)malonic acid
diethyl ester
a) l-Benzyl-4-(4'-trifluoromethylbiphenyl-2-
carbonylamino)piperidine

4 '-Trifluoromethyl-biphenyl-carboxylic acid (5.0 g) was
dissolved in dimethylformamide (50 mL), and to this solution
were added at room temperature 4-amino-l-benzylpiperidine
(3 . 55 g) , 1-hydroxybenzotriazole hydrate (3.0 g) and l-ethyl-3-
(3'-dimethylaminopropyl)carbodiimide hydrochloride (3.58 g).
The mixture was stirred at room temperature overnight, and the
reaction solution was concentrated in vacuo to precipitate
crystals. The crystals were washed successively with
saturated aqueous sodium bicarbonate and water, and dried in
vacuo to give the title compound (7.42 g).
b) 4-(4'-Trifluoromethylbiphenyl-2-carbonylamino)piperidine

To a solution of the l-benzyl-4-(4'-
trifluoromethylbiphenyl-2-carbonylamino)piperidine (1.47 g)
obtained in Example 8 a) in tetrahydrofuran-methanol (1:1; 50
mL) was added palladium hydroxide (300 mg) in a stream of argon
under ice-cooling. The mixture was stirred for one day at
normal pressure under hydrogen atmosphere, and further stirred
for one day at normal pressure under hydrogen atmosphere after
further addition of palladium hydroxide (300 mg) . The reaction
mixture was filtered through a Celite pad and washed with
methanol. The filtrate and the washings were combined,
concentrated in vacuo and purified by column chromatography on
silica gel with chloroform:methanol:aqueous ammonia=100:10:1
to give the title compound (1.03 g).
c) [4-(4'-Trifluoromethylbiphenyl- 2 -carbonyl-
amino)piperidin-l-yl]acetic acid ethyl ester

To a solution of 4-(4'-trifluoromethylbiphenyl-
2-carbonylamino)piperidine (1.03 g) obtained in Example 8 b)
in dimethylf ormamide ( 5 mL ) were added potassium carbonate (276
mg) and bromoacetic acid ethyl ester (223 mL) . The mixture was
stirred overnight at ambient temperature of 90°C, and then
concentrated in vacuo. The residue was distributed with water
and chloroform, and the aqueous layer was further extracted with
chloroform. The organic layers were combined, washed with
saturated brine, dried over sodium sulfate, concentrated in
vacuo and purified by column chromatography on silica gel with
chloroform:methanol=30:1 to give the title compound (598 mg).
d) [4-(4'-Trifluoromethylbiphenyl-2-carbonyl-
amino)piperidin-l-yl]acetic acid

To a solution of [4-(4'-trifluoromethylbiphenyl-
2-carbonylamino)piperidin-l-yl]acetic acid ethyl ester (595
mg) obtained in Example 8 c) in tetrahydrofuran-methanol (1:2;
10.2 mL) was added 1M aqueous lithium hydroxide (6.8 mL), and
the mixture was stirred at room temperature for 6 hours. The
reaction solution was concentrated in vacuo and 2N hydrochloric
acid was added to the residue to adjust the pH to about 3, thereby
crystals were precipitated. The crystals were collected by
filtration, washed with cold water and dried in vacuo to give
the title compound (411 mg).
e ) 2 -Phenyl-2-(2-{4-[(4'-trifluoromethylbiphenyl- 2 -
carbonyl)amino]piperidin-1-yl}acetoxymethyl)malonic acid
diethyl ester
The [4 -(4'-trifluoromethylbiphenyl-2-carbonyl-
amino)piperidin-1-yl]acetic acid obtained in Example 8 d) and
the 2-hydroxymethyl-2-phenylmalonic acid diethyl ester
obtained in Example l'-2 a) were subjected to reactions similar
to those in Example 1 g) to give the title compound (90 mg) (see
Table 58).

Example 9
2-Phenyl-2-(2-{4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]indol-l-yl}acetoxymethyl)malonic acid diethyl
ester
a) (4-Nitroindol-1-yl)acetic acid ethyl ester

Sodium hydride (60% /mineral oil: 81 mg) was dissolved in
dimethylformamide (5 mL), and the solution was cooled to 0°C.
After addition of 4-nitroindole (300 mg) , the mixture was
stirred for one hour, and bromoacetic acid ethyl ester (340 mg)
was added thereto, followed by stirring at 0°C for 4 hours.
Water was added thereto and the mixture was concentrated,
diluted with ethyl acetate, washed with water, dried over sodium
sulfate, then concentrated to give the title compound (367 mg) .
b) (4-Nitroindol-1-yl)acetic acid

The (4-nitroindol-1-yl)acetic acid ethyl ester
obtained in Example 9 a) was subjected to reactions similar to
those in Example 1 f) to give the title compound (243 mg).
c) 2-[2-(3-Nitroindol-1-yl)acetoxymethyl]-2-phenylmalonic
acid diethyl ester

The (4-nitroindol-l-yl(acetic acid (229 mg) obtained in
Example 9 b), 4-dimethylaminopyridine (143 mg) and the
2-hydroxymethyl-2-phenylmalonic acid diethyl ester (240 mg)
obtained in Example 1-2 a) were subjected to reactions similar
to those in Example 1-3 c) to give the title compound (301 mg) .
d) 2-[2-(4-Aminoindol-l-yl)acetoxymethyl]-2-phenylmalonic
acid diethyl ester

The 2-[2-(3-Nitroindol-l-yl)acetoxymethyl]-2-
phenylmalonic acid diethyl ester (100 mg) obtained in Example
9 c) was dissolved in tetrahydrofuran (2 mL), ethanol (4 mL)
and water (1 mL), and to the solution were added ammonium
chloride (57 mg) and reduced iron (60 mg) . The mixture was
stirred at 100°C for 2 hours, cooled, and filtered through a
Celite pad. The filtrate was concentrated and diluted with
ethyl acetate. The extract was washed successively with
saturated aqueous sodium bicarbonate, water and saturated brine ,
dried over sodium sulfate, and concentrated to give the title
compound (93 mg).
e) 2-Phenyl-2-(2-{4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]indol-l-yl}acetoxymethyl)malonic acid diethyl
ester

phenylmalonic acid diethyl ester obtained in Example 9 d) was
treated in a similar manner to Example 1 e) to give the title
compound (119 mg)(see Table 59).
Example 9-2
2-(2-{2-methyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl}amino]benzimidazol-l-yl}acetoxymethyl)-2-phenyl-
malonic acid diethyl ester
a) 2-Methyl-4-nitro-lH-benzimidazole

3-Nitrobenzene-l,2-diamine (1.0 g) was dissolved in
ethanol (90 mL) and 5N hydrochloric acid (24 mL), and to this
solution was added 2,4-pentanedione (1.3 g) . The mixture was
heated for 3 hours under reflux, cooled down to room temperature
and concentrated. To this concentrate was added ethyl acetate,
and the mixture was washed successively with saturated aqueous
sodium bicarbonate and water, and dried over sodium sulfate to
give the title compound (1.1 g).
b) ( 2-Methyl-4-nitrobenzimidazol-l-yl)acetic acid ethyl ester

The 2-methyl-4-nitro-1H-benzimidazole (1.1 g) obtained
in Example 9-2 a) was subjected to reactions similar to those
in Example 9 a) to give the title compound (1.44 g).
c) 2-(2-{2-Methyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]benzimidazol-1-yl}acetoxymethyl)-2 -phenyl-
malonic acid diethyl ester

The (2-Methyl-4-nitrobenzimidazol-l-yl)acetic acid
ethyl ester (500 mg) obtained in Example 9-2 b) was subjected
to reactions similar to those in Examples 9 d), 1d), 1 e), 1
f) and 1 g) to give the title compound (152 mg) (see Table 59).
Example 9-3
[2-Oxo-3-(4'-trifluoromethylbiphenyl-2-carbonyl)-2,3-
dihydrobenzoxazol-6-yl]acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester
The {3-Hydroxy-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2-
phenylethyl ester (195 mg) obtained in Example 3-2 was dissolved
in chloroform (5 mL), and to this solution was added
triethylamine (72 mg) . The solution was cooled to 0°C and
triphosgene (35 mg) was added thereto. After stirring for one
hour, the reaction solution was washed with water, dried over
sodium sulfate and purified by column chromatography on silica
gel with hexane:ethyl acetate=l:l to give the title compound
(173 mg)(see Table 59).
Example 9-4
2-(2-{3-Ethoxycarbonyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid
diethyl ester
a) 5-Chloro-2-nitrobenzoic acid chloride

5-Chloro-2-nitrobenzoic acid was subjected to reactions
similar to those in Example 1 d) to give the title compound.
b) 5-Chloro-2-nitrobenzoic acid ethyl ester
To a mixture of ethanol (1.23 mL), triethylamine (3.05
mL) and tetrahydrofuran (35 mL) was dropwise added a solution
of 5-chloro-2-nitrobenzoic acid chloride (4.44 g) obtained in
Example 9-4 a) in tetrahydrofuran (10 mL) under ice-cooling.
The mixture was stirred at room temperature overnight, and water
was then added. The solution was diluted with ethyl acetate,
and the organic layer was washed successively with saturated
aqueous sodium bicarbonate and saturated brine, dried over
sodium sulf ate and concentrated to give the title compound (4.43
g) as a pale brown solid.
c) 3-Ethoxycarbonyl-4-nitrophenylmalonic acid dibenzyl ester

The 5-chloro-2-nitrobenzoic acid ethyl ester (4.40 g)
obtained in Example 9-4 b) and malonic acid dibenzyl ester were
subjected to reactions similar to those in Example 1-3 a) to
give the title compound (4.61 g).
d) 4-Amino-3-ethoxycarbonylphenylacetic acid

The 3-ethoxycarbonyl-4-nitrophenylmalonic acid
dibenzyl ester (1.51 g) obtained in Example 9-4 c) was subjected
to reactions similar to those in Example 1-3 d) to give the title
compound (4.59 g).
e) 3-Ethoxycarbonyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenylacetic acid

The 4-amino-3-ethoxycarbonylphenylacetic acid (1.51 g)
obtained in Example 9-4 d) and
4'-trifluoromethylbiphenyl-2-carboxylic acid chloride (1.99
g) were subjected to reactions similar to those in Example 7
a) with the proviso that sodium bicarbonate was used as a base,
thereby the title compound (1.87 g) was given as a pale yellow
amorphous powder.
f) 2-(2-{3-Ethoxycarbonyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)amino]phenyl}acetoxymethyl)- 2-phenylmalonic acid
diethyl ester
The 3-ethoxycarbonyl-4-[ ( 4 ' -trif luoromethylbiphenyl-
2-carbonyl)amino]phenylacetic acid (0.532 g) obtained in
Example 9-4 e) and the 2-hydroxymethyl-2-phenylmalonic acid
diethyl ester (1.04 g) obtained in Example 1-2 a) were treated
in a similar manner to Example 1 g) to give the title compound
(0.524 g)(see Table 59).
Example 9-5
2-(3-{3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-
carbonyl)-amino]-phenyl}-propionyloxymethyl)-2-phenyl-
malonic acid diethyl ester
a) 5-Methyl-2-nitrobenzoic acid chloride

5-Methyl-2-nitrobenzoic acid was treated in a similar
manner to Example 1d) to give the title compound.
b) 5,.N, N-Trimethyl-2-nitrobenzamide
The 5-methyl-2-nitrobenzoic acid chloride obtained in
Example 9-5 a) was treated in a similar manner to Example 1
e) to give the title compound.
c) 5-Bromomethyl-N,N-dimethyl-2-nitrobenzamide

The 5, N, N-Trimethyl-2-nitrobenzamide (4.16 g) obtained
in Example 9-5 b) , N-bromosuccinimide (3.56 g) and
2,2'-azobisisobutyronitrile (328 mg) were suspended in carbon
tetrachloride (80 mL) . The suspension was stirred at 90°C for
2 hours, filtered through a Celite pad and purified by column
chromatography on silica gel with hexane:ethyl acetate=5:4 to
give the title compound (602 mg).
d) 3-(3-Dimethylcarbamoyl-4-nitrophenyl)-2-methoxy-
carbonylpropionic acid benzyl ester

The 5-bromomethyl-N,N-dimethyl-2-nitrobenzamide (0.597
g) obtained in Example 9-5 c) and malonic acid benzyl ester
methyl ester were subjected to reactions similar to those in
Example 9-4 c) to give the title compound (0.491 g).
e) 3-(4-Amino-3-dimethylcarbamoylphenyl)-2-methoxycarbonyl-
propionic acid

The 3-(3-dimethylcarbamoyl-4-nitrophenyl)-2-
methoxycarbonyl-propionic acid benzyl ester (0.490 g) obtained
in Example 9-5 d) was subjected to reactions similar to those
in Example 1-2 c) to give the title compound (0.353 g) .
f) 3-(4-Amino-3-dimethylcarbamoylphenyl)propionic acid
methyl ester

The 3-(4-amino-3-dimethylcarbamoylphenyl)-2-
methoxycarbonylpropionic acid (34 7 mg) obtained in Example 9-5
e) was stirred at 150°C for 40 minutes, cooled down to room
temperature, and purified by column chromatography on silica
gel with hexane:ethyl acetate (1:1 to 0:1) to give the title
compound (180 mg).
g) 2 - ( 3 - { 3 -Dimethylcarbamoyl- 4 -[(4'-trifluoromethy1-
biphenyl-2 -carbonyl)amino]phenyl}propionyloxymethyl) - 2 -
phenylmalonic acid diethyl ester
The 3-(4-amino-3-dimethylcarbamoylpheny1)propionic
acid methyl ester (0.138 g) obtained in Example 9-5 f) was
subjected to reactions similar to those in Examples 1 e) , 1f)
and 1 g) to give the title compound (0.158 g)(see Table 59).
Examples 9-6 to 9-29
Compounds of Examples 9-6 to 9-29 were obtained in a
similar manner to Examples 9 to 9-5. The compounds thus
obtained were shown in Tables 59 to 64.

melted and sealed by the rotation of the die rolls, then the
capsules were cut from the film. The capsules were dried in
a rotary dryer, and allowed to dry for 4 days to give soft
capsules. Hereinafter, specific examples of formulations were
given.
Formulation 1-1
(a) film composition
gelatin 100 parts
sugar alcohol solution derived from corn starch
30 parts
purified water 100 parts
(b) filling solution (per capsule)
propylene glycol fatty acid ester 295 mg
ethanol 105 mg
Formulation 1-2
(a) film composition
gelatin 100 parts
sugar alcohol solution derived from corn starch
30 parts
purified water 100 parts
(b) filling solution (per capsule)
compound of Example 2-5 5 mg
propylene glycol fatty acid ester 291 mg
ethanol 104 mg
Formulation 1-3
(a) film composition
gelatin 100 parts
sugar alcohol solution derived from corn starch
30 parts
purified water 100 parts
(b) filling solution (per capsule)
compound of Example 2-5 5 mg
propylene glycol fatty acid ester 277 mg
ethanol 148 mg
Formulation 2
The compound of Example 2-22, an excipient and a binder
were mixed in a usual method to prepare granulated powder. The
powder obtained was blended with a disintegrator and a lubricant
to prepare a powder for tablets in a usual method. The powder
was compressed to give tablets in a usual method. Specific
examples of formulations were hereinafter given.
Formulation 2-1
compound of Example 2-22 5 mg
lactose 133.06 mg
crystalline cellulose 18 mg
hydroxypropyl methylcellulose 2910 5.4 mg
crospovidone 18 mg
magnesium stearate 0.54 mg
Formulation 2-2
compound of Example 2-22 5 mg
lactose 92.44 mg
corn starch 15 mg
hydroxypropyl methylcellulose 2910 3.6 mg
carboxymethyl starch 3.6 mg
magnesium stearate 0.36 mg
Formulation 2-3
compound of Example 2-22 5 mg
D-mannitol 158.4 mg
hydroxypropyl methylcellulose 2910 6 mg
calcium silicate 20 mg
crospovidone 10 mg
magnesium stearate 0.6 mg
Pharmacological test
Test Example 1
Inhibition of interliposomal triglyceride (TG) transfer
activity by MTP
Microsomal triglyceride transfer protein (MTP) from
bovine liver was partially purified in such a way described
below. A buffer (50 mM Tris, 250 mM sucrose, 1 mM EDTA, 0.02%
NaN3 (pH 7.4)) for making a homogenate preparation was added
to bovine liver, and the mixture was homogenated under
ice-cooling, then centrifuged at 10,000 x g (4°C, 30 minutes) .
The supernatant was adjusted to pH 5.1 with hydrochloric acid,
and stirred for 30 minutes. The solution was further
centrifuged at 10 , 000 x g ( 4°C, 30 minutes ) , and 1 mM Tris buffer
was added to the precipitated residue, and the mixture was
adjusted to pH 8.6 with sodium hydroxide. After addition of
2 . 7M ammonium sulfate solution, the mixture was stirred for 30
minutes, then centrifuged at 10,000 x g (4°C, 40 minutes) . The
resulting supernatant was served as a crude extraction fraction
of MTP and stored at -80°C under freezing. In its practical
use, the crude extraction fraction of MTP was purified by column
chromatography on diethylaminoethyl (DEAE) Sepharose using
FPLC (Fast Performance Liquid Chromatography) system, and the
purified MTP was used for the test.
Small unilamellar-vesicle (SUV) liposome (donor, 0.25
mol% triolein, 5 mol% cardiolipin) labeled with 14C-triolein
and non-labeled SUV liposome (acceptor, 0.25 mol% triolein)
were prepared. A fixed amount of donor and acceptor, and MTP
were mixed with a sample dissolved in DMSO or with DMSO. The
mixture was incubated in a 15 mM Tris hydrochloride buffer (pH
7.4) containing 40 mM sodium chloride, 1 mM EDTA
(ethylenediaminetetraacetic acid), 0.02% NaN3 and 0.5% bovine
serum albumin at 37°C for one hour. After completion of the
incubation, a suspension of DEAE cellulose (50% v/v) in 15 mM
Tris hydrochloride buffer (pH 7.4) was added to the above
solution, and the mixture was centrifuged to separate the donor
and the acceptor. The radioactivity in the acceptor was
measured by liquid scintillation counter. The value obtained
by subtracting the radioactivity in the blank from the amount
of radioactivity in the acceptor of a DMSO group was determined
as MTP-mediated TG transfer activity, and it was compared with
the value obtained by subtracting the radioactivity in the blank
from the radioactivity in a sample group. The blank was
prepared by adding 15 mM Tris-HCl buffer (pH 7.4) in place of
MTP. Inhibition rate (%) was calculated from the values
obtained according to the following equation.
Inhibition rate (%) = 100 x (1 minus ((radioactivity of
sample group minus radioactivity of blank group)/
(radioactivity of DMSO group minus radioactivity of blank
group))).
50% Inhibition rate (IC50) was determined on the basis
of the above equation. The results were shown in Table 6 6 to
70.
Test Example 2
Inhibition of apolipoprotein B secretion from HepG2 cells
HepG2 cells were suspended in Dulbecco' s Modified Eagle' s
Medium (DMEM)(containing 10% fetal bovine serum, 100 units/mL
penicillin and 100 ng/mL streptomycin) , and placed on a 96-well
plate (4 x 104 cells/well), then incubated for 24 hours. After
removal of the medium, DMEM was replaced by a medium containing
a sample dissolved in DMSO or a medium containing DMSO
(concentration of DMSO: 0.5%) and incubation was further
performed for 24 hours, after which the supernatant was
recovered, and concentration of apo B in the supernatant was
assayed by Enzyme-Linked Immunosorbent Assay (ELISA)
ELISA was carried out as follows. Anti-human apo B
monoclonal antibody (0.5 mg/well) diluted with a solution of
sodium carbonate in sodium bicarbonate buffer (50 mL, pH 9.6)
was placed in a 96-well plate for ELISA, and allowed to stand
at room temperature for 15 hours. After washing the plate, a
blocking solution (250 mL/well) was placed in the well, and
allowed to stand at room temperature for 1.5 hours. After
washing the plate, a standard and a sample (100 mL/well) were
placed in the well and allowed to stand at room temperature
for one hour. The standard was prepared by adjusting the
concentration of the purified human apo B with the DMEM to 0
to 1000ng/mL. After washing the plate, an anti-human apo B
polyclonal antibody labeled with a horse radish peroxidase
which was diluted in 1:1000 with DEME (100 mL/well) , and allowed
to stand at room temperature for one hour. After washing the
plate, 2,2-azinobis(3- ethylbenzothiazoline-6-sulfonic acid)
solution (100 mL/well) was placed in the well, and allowed to

stand at room temperature for one hour. The reaction was
stopped by addition of 2% oxalic acid (100 mL / well), and
absorbency at 405 nm was measured. Concentration of apo B in
the sample was calculated on the basis of a standard curve of
the standard. Inhibition rate (%) was calculated from the
assayed values in accordance with the following equation.
Inhibition rate (%) = 100 x (1 minus (concentration of
apo B in sample group/concentration of apo B in DMSO group) .
Based on the above equation, 50% inhibition concentration
(IC50) was determined.
The results were shown in Tables 66 to 70.

Test Example 3
Olive oil-loading test
Syrian hamsters (9-11 weeks of age) under non-fasted
conditions were used in the test. Blood was collected
previously from orbital venous plexus, and a sample was
suspended in 0.5% methyl cellulose (vehicle) and the suspension
was forced to be administered orally to the hamsters at a dose
of 0.3, 1, 3 or 10 mg/2 mL/kg. Only vehicle in the same volume
was administered to the control group. Olive oil (2 mL/kg) was
forced to be administered orally 30 minutes after the
administration of the sample, and blood was collected from
orbital venous plexus 4 hours later. Plasma was recovered from
the blood, and the amount of triglyceride (TG) in the plasma
was determined by automatic analyzer (Hitachi Co.). The data
was expressed in terms of ATG(mg/dL)=the value at 4th hr minus
the value before administration. Inhibition rate (%) was
calculated from the data obtained on the basis of the following
equation.
Inhibition rate ( % ) =100 x (1 minus ATG of sample group/ATG
of control group). The results were shown in Table 71.

Test Example 4
Liver TG release inhibition test
Syrian hamsters (9 to 11 weeks of age) which were fasted
for one day were used in the test.
Blood was collected previously from orbital venous plexus, and
a sample was forced to be administered orally to the hamsters
at a dose of 30, 100 or 300 mg/2 mL/kg, and the same amount of
vehicle was administered to the control group. Triton WR 1339
(2 mL/kg) was intravenously administered to the hamsters 30
minutes after the above administration. Two hours later, blood
was collected from orbital venous plexus, and plasma was
separated from the blood. The amount of TG in the plasma was
determined by automatic analyzer (Hitachi Co.). The data was
expressed in terms of TG release velocity (mg/dL/min)=(value
at 2nd hour minus value before administration) /120 . Inhibition
rate (%) was calculated from the data obtained on the basis of
the following equation.
Inhibition rate (%) = 100 x (1 minus TG release velocity of
sample/TG release velocity of control group) . The results were
shown in Table 72.
was collected from auricular artery 6 hours after the feeding
on the 4th day of the administration, and cholesterol level in
plasma was assayed. In the table, increased amount of plasma
cholesterol during from the time of grouping to the 4th day was
shown.

Test Example 6
Determination of the concentration in plasma
Syrian hamsters (9-15 weeks of age) under non-fasted
conditions were used in the test. A sample was suspended in
0.5% methyl cellulose (vehicle), and the suspension was forced
to be administered orally to the hamsters at a dose of 30 or
100 mg/2 mL/kg. After a fixed period of time, blood was partly
collected from orbital venous plexus, and the hamsters were
subjected to laparotomy under ether anesthesia, and then blood
was collected from portal vein. The blood was immediately
cooled with ice to separate plasma. A portion of the plasma
was extracted with an organic solvent and the supernatant was
recovered. Concentration of the sample (unchanged form) and
that of the metabolite in the supernatant were determined
quantitatively by high performance liquid chromatography/mass
spectrometry (LC/MS) comparing with chromatogram of synthetic
standard.

Test Example 7
Metabolic stability test in liver S9 and small intestine S9
Human and hamster liver S9 (final concentration: 2 mg
protein/mL), and human and hamster small intestine S9 (final
concentration: 2 mg protein/mL) were each suspended in 100 mM
potassium phosphate buffer (pH 7.4, containing b-nicotinamide
adenine dinucleotide phosphate: 1.3 mM, D-glucose-6-
phosphate: 3.3 mM, magnesium chloride: 3.3 mM,
glucose-6-phosphate dehydrogenase :0.4 U/mL ) . The suspensions
were mixed with a solution of a sample (Example 2-5) in DMSO.
The solutions were incubated at 37°C for 0, 10 and 60 minutes,
and an organic solvent was added thereto. The solutions were
centrifuged, and the concentration of the sample (unchanged
form) in the supernatant was determined by high performance
liquid chromatography/mass spectrometry (LC/MS) . Based on the
data obtained, remaining rate (%) was calculated according to
the following equation.
Remaining rate(%)=amount of sample 10 or 60 minutes after
incubation/amount of sample at zero time after incubation x 100

Test Example 8
Inhibitory activity on MTP and apo B secretion inhibition by
metabolites
In a similar manner to Test Examples 1 and 2 , the activity
of metabolites was assayed. The results were shown in Table
Industrial Applicability
It is apparent from the above Test Examples 1 to 3 that
novel compounds and their pharmaceutically acceptable salts
of the present invention possess excellent MTP inhibition
activity and also strongly inhibit absorption of triglyceride.
In addition, as is apparent from Test Example 4, even when
compounds of the present invention are administered at high
dose, inhibition rate of liver TG release is 18-19 % or lower,
more effectively 9 % or lower, especially effectively 0 % or
lower, and thus the compounds of the present invention inhibit
little of liver TG release. Further, Test Example 6 reveals
that active compounds after absorption in the small intestine
are present in portal vein in a very small amount, and since
most (8-fold to 80-fold amount) of such active compounds are
metabolites, they do not reach the liver. Furthermore, it is
deduced from Test Example 7 that a small amount of active
compound which has reached the liver is metabolized rapidly
to a metabolite. In addition. Test Example 8 proves that ester
moiety of these metabolites is cleaved by hydrolysis and thus
they have little or no MTP inhibitory activity. Further, Test
Example 5 reveals that combination use of the compounds of the
present invention with other agents for treating
hyperlipidemia (statin type agents) can remarkably inhibit the
increase of cholesterol and exhibit extremely excellent
synergistic effect. These facts elucidate that the compounds
of the present invention can be used in combination with other
agents, particularly other agents for treating hyperlipidemia,
arteriosclerosis, coronary artery diseases, obesity, diabetes
or hypertension.
From the fact as mentioned above, it is understood that
novel compounds of the present invention and their
pharmaceutically acceptable salts can inhibit lipid
absorption in the small intestine and further do not inhibit
TG release in the liver. This means that the compounds of this
invention do not inhibit MTP in the liver, but selectively
inhibit MTP in the small intestine.
Therefore, selective inhibition of MTP activity in the
small intestine by the compounds of the present invention should
lower lipid absorption, which makes it possible to control
lipoproteins such as triglyceride, cholesterol and LDL, etc.
in blood or to control lipid in cells. Further, since the
compounds of the present invention do not affect liver MTP,
accumulation of triglyceride does not occur in the liver.
Consequently, inhibition of fatty liver generation as an
adverse effect might be expected. Therefore, the compounds of
the present invention can be said novel MTP inhibitors having
no side effects such as a fatty liver, etc. or, in other words,
they are novel agents for the treatment or prophylaxis of
hyperlipidemia, arteriosclerosis, coronary artery diseases,
obesity, diabetes or hypertension, and further for the
treatment or prophylaxis of pancreatitis,
hypercholesterolemia, hypertriglyceridemia, etc., which
rarely act on MTP in the liver and do substantially inhibit only
MTP in the small intestine.
We claim:
1. An ester compound represented by the formula (1)

wherein
R1 and R2 are each hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-
C6 alkoxy, halo C1-C6 alkyl, halo C1-C6 alkyloxy, C6-C14 aryl which is
unsubstituted or substituted by 1 to 3 substituent(s) selected from Cp
C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, Cp
C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl) amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido, C7-C16 aralkyl which is unsubstituted or substituted by 1 to
3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylamino, di(C1-C6 alkyl) amino, carboxyl, C2-C7 alkoxycarbonyl,
amido, trifluoromethyl, C1-C6 alklsulfonyl, aminosulfonyl, C3-C7
cycloalkyl, phenyl and acylamido, C1-C6 aryloxy which is
unsubstituted or substituted by 1 to 3 substituent(s) selected from Cp
C6 alkoxy, halogen, nito, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto,
C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino,
carboxyl, C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6
alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido, C7-C16 aralkyloxycy which is unsubstituted or substituted
by 1 to 3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6
alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto,
C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl) amino,
carboxyl, C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6
alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido, C7-C5 arylcarbonyl which is unsubstituted or substituted
by 1 to 3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6
alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto,
C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino,
carboxyl, C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6
alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido, heterocycle which is unsubstitutbed or substituted by 1 to
3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino, carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, C2-C7
alkoxycarbonyl, halogen, C2-C6 alkenyl, -N(R40) (R41) wherein R40
and R41 are each independently hydrogen or C6-C14 aryl which is
unsubstituted or substituted by 1 to 3 substituent(s) selected from C1-
C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl) amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido;
ring A is C6-C14 aryl, heterocycle, or

X is -COO- (CH2)n-, -CON(R10)-(CH2)n - or -N((R10) -CO- (CH2)n-
wherein R10 is hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl and n is an
integer of 0 to 3;
R3 and R4 are each independently hydrogen, hydroxy, halogen, C1-C6
alkyl which is unsubstituted or substituted by 1 to 5 substituent(s)
selected from halogen, carboxyl, hydroxy, amino, nitro, cyano C1-C6
alkoxy, C7-C16 aralkyloxy, C2-C7 alkoxycarbonyl, C6-C14 aryl, C1-C6
alkykthio, C1-C6 alkylsulfinyl, C1C6 alkylsulfonyl, C1C6 alkylamino
and acylamino, C1C6 alkoxy, halo C1-C6 alkyl, C7-C16 aralkyloxy, C1-
C6 acyl, heterocycle which is unsubstituted or substituted by 1 to 3
substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino, carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, -CON(Rn)
(R12) (wherein R11 and R12 are each independently hydrogen, C1-C6
alkyl, C6-C14 aryl which is unsubstituted or substituted by 1 to 3
substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapta, C1-C6
alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, C7-C16
aralkyl which is unsubstituted or substituted by 1 to 3 substituent(s)
selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro,
cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino,
C1-C6 alkylamino, di(C1-C6 alkyl)amino carboxyl, C2-C7
alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, C1-C6
alkoxy, or R11 and R12 may be take together with the nitrogen to which
they are attached to form

wherein p is an integer of 0 to 2), - (CH2)q-N(R13) (R14) (wherein R13
and R14 are each independently hydrogen, C1-C6 alkyl, C2-C7
alkoxycarbonyl, C1-C6 acyl, or R13 and R14 may be taken together with
the nitrogen to which they are attached to form

wherein p has the same meaning as defined above and q is an integer
of 0 to 3), or -CO(R15) (wherein R15 is hydroxy, C1-C6 alkoxy, C6-C14
aryloxy which is unsubstituted or substituted by 1 to to 3
substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, C7-C16
aralkyloxy which is unsubstituted or substituted by 1 to to 3
substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido, or C1-C6
alkyl);
ring B is
wherein K is an integer of 0 to 2, or ring B may be taken together with R3,
R10 and the nitrogen bound to R10 to form

Alk1 is alkanediyl or alkenediyl;
Alk2 is alkanediyl or alkenediyl;
1 is an integer of 0 to 3;
m is an integer of 0 to 3;
D is the group represented by the following formula

(wherein R5, R6 and R7 are each independently hydrogen, C1-C6 alkyl,
C1-C6 alkoxy, C2-C7 alkoxycarbonyl, carboxyl, halogen, cyano, nitro,
halo C1-C6 alkyl, C1-C6 acyl, hydroxy, C6-C14 aryl which is
unsubstituted or substituted by 1 to to 3 substituent(s) selected from
C1-C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, or -CON(R16) (R17) (wherein R16 and R17 are
each independently hydrogen, C1-C6 alkyl or halo C1-C6 alkyl and r is
an integer of 0 to 3);
ring C is C6-C14 aryl, heterocycle residue or C3-C7 cycloalkyl;
and
R8 and R9 are each independently -CON(R18) (R19) (wherein R18 and
R19 are each independently hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl,
halo C1-C6 alkyl, C2-C12 alkoxyalkyl or C6-C14 aryl which is
unsubstituted or substituted by 1 to to 3 substituent(s) selected from
C1-C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido) or -COO(R20) (wherein R20 is hydrogen, C1-C6
alkyl or C3-C7 cycloalkyl) or a pharmaceutically acceptable salt.
2. The ester compound or a pharmaceutically acceptable salt as claimed
in claim 1, wherein the ring C is

in which q is an integer of 0 to 3.
3. The ester compound or a pharmaceutically acceptable salt as claimed
in claim 2, wherein ring B is
4. The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 3, wherein ring A is

5. The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 4, wherein X is -CON(R10) - (CH2)n- in which R10 and n each
has the same meaning as defined above.
6. The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 4, wherein X is -COO-(CH2)n- in which n has the same
meaning as defined above.
7. The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 5 or claim 6, wherein n is 0.
8. An ester compound represented by the formula (1)
wherein
R1 and R2 are each hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6
alkotfy, halo C1-C6 alkyl, halo C1-C6 alkyloxy, C6-C14 aryl which is
unsubstituted or substituted by 1 to 3 substitutent(s) selected from C1-
C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, C7-C16 aralkyl which is unsubstituted or
substituted by 1 to 3 substituent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-
C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, C6-C14 aryloxy which is unsubstituted or
substituted by 1 to 3 substituent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-

C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, C7-C16 aralkyloxy which is unsubstituted or
substituted by 1 to 3 substituent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-
C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbony, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, C7-C15 arylcarbonyl which is unsusbstituted or
substituted by 1 to 3 substitutent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-
C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, heterocycle which is unsubstituted or
substituted by 1 to 3 substituent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-
C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido;
ring A is C6-C14 aryl, heterocycle, or
X is -COO- (CH2)n- or -CON(R10) - (CH2)n- wherein R10 is
hydrogen, C1-C6 alkyl or C3-C7 cycloalkyl and n is an integer of 0 to
3;
R3 and R4 are each independently hydrogen, hydroxy, halogen, C1-C6
alkyl, C1-C6 alkoxy, halo, C1-C6 alkyl, -CON(Rn) (R12) (wherein R11
and R12 are each independently hydrogen, C1-C6 alkyl, C6-C14 aryl
which is unsubstituted or substituted by 1 to 3 substituent(s) selected
from C1-C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6
acyl, C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6
alkylamino, di(C1-C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl,
amido, trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7
cycloalkyl, phenyl and acylamido, C7-C16 aralkyl which is
unsubstituted or substituted by 1 to 3 substituent(s) selected from C1-
C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino, carboxyl, C2-C7 alkoxy carbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, or R11 and R12 may be taken together with the
nitrogen to which they are attached to form
wherein p is an integer of 0 to 2), -N(R13) (R14) (wherein R13 and R14
are each independently hydrogen, C1-C6 alkyl, or R13 and R14 may be
taken together with the nitrogen to which they are attached to form

wherein p has the same meaning as defined above), or -CO(R15)
(wherein R15 is hydroxy, C1-C6 alkoxy, C6-C14 aryloxy which is
unsubstituted or substituted by 1 to 3 substituent(s) selected from C1-
C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, or C7-C16 aralkyloxy which is unsubstituted or
substituted by 1 to3 substituent(s) selected from C1-C6 alkyl, hydroxy,
C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy,
mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-C6
alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido, trifluoromethyl,
C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido);
ring B is
wherein K is an integer of 0 to 2, or ring B may be taken together with R3,
R10 and the nitrogen bound to R10 to form

Alk1 is alkanediyl or alkenediyl;
Alk2 is alkanediyl or alkenediyl;
1 is an integer of 0 to 3;
m is an integer of 0 to 3;
D is the group represented by the following formula

(wherein R5, R6 and R7 are each independently hydrogen, C1-6 alkyl, C1-6
alkoxy, C2-C7 alkoxycarbonyl, carboxyl, halogen, cyano, nitro, halo C1-C6
alkyl, C1-C6 acyl, hydroxyl, C6-C14 aryl which is unsubstituted or substituted
by 1 to 3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, or -CON(R16) (R17) (wherein R16 and R17 are
each independently hydrogen, C1-C6 alkyl or halo C1-C6 alkyl);
ring C is C6-C14 aryl, heterocycle residue or C3-C7 cycloalkyl; and
R8 and R9 are each independently -CON(R18) (R19) (wherein R18 and
R19 are each independently hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl,
halo C1-C6 alkyl, C2-C12 alkoxyalkyl or C6-C14 aryl which is
unsubstituted or substituted by 1 to to 3 substituent(s) selected from
C1-C6 alkyl, hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl,
C1-C6 acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino,
di(C1-C6 alkyl)amino carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido) or -COO(R20) (wherein R20 is hydrogen, C1-C6
alkyl or C3-C7 cycloalkyl)), or a pharmaceutically acceptable salt.
9. The ester compound or a pharmaceutically acceptable salt as claimed
in claim 8, wherein R and R each is phenyl which is unsubstituted or
substituted by 1 to 3 substituent(s) selected from C1-C6 alkyl,
hydroxy, C1-C6 alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6
acyloxy, mercapto, C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-
C6 alkyl)amino, carboxyl, C2-C7 alkoxycarbonyl, amido,
trifluoromethyl, C1-C6 alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl,
phenyl and acylamido, naphthyl which is unsubstituted or substituted
by 1 to 3 substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6
alkoxy, halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto,
C1-C6 alkylthio, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino,
carboxyl, C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6
alkylsulfonyl, aminosulfonyl, C3-C7 cycloalkyl, phenyl and
acylamido, or biphenyl which is unsubstituted or substituted by 1 to 3
substituent(s) selected from C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
halogen, nitro, cyano, C1-C6 acyl, C1-C6 acyloxy, mercapto, C1-C6
alkylthio, amino C1-C6 alkylamino, di(C1-C6 alkyl)amino, carboxyl,
C2-C7 alkoxycarbonyl, amido, trifluoromethyl, C1-C6 alkylsulfonyl,
aminosulfonyl, C3-C7 cycloalkyl, phenyl and acylamido; C6-C14 aryl
represented by ring A is phenyl, naphthyl, or biphenyl.
10.The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 1, which is represented by the formula (1')

Wherein
R2 and R2" are each independently hydrogen, C1-C6 alkyl, C3-C7
cycloalkyl, C1-C6 alkoxy, halogen, halo C1-C6 alkyl, C1-C6 acyl, C2-C6
alkenyl or cyano;
X, is -O- or -NH10- wherein R10 is hydrogen, C1-C6 alkyl or C3-C7
cycloalkyl; and
R1, R3, R4, R5, R6, R7, R8, R9, ring C, 1 and m each has the same
meaning as defined above,
or a pharmaceutically acceptable salt.
11 .The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 10, wherein the ring C is

in which q is an integer of 0 to 3.
12.The ester compound, or a pharmaceutically acceptable salt as claime
in claim 11, wherein X1 is-NR10- in which R10 has the same meaning
as defined above (
13.The ester compound, or a pharmaceutically acceptable salt as claimed
in claim 11, wherein X1 is -O-.
14.The ester compound, or a pharmaceutically acceptable salt as claimed
in any of the claims 10 to 13, wherein the group -(CH2)1- is located at
the h-position of the benzene ring in the formula (1').
15.The ester compound, or a pharmaceutically acceptable salt as claimed
in any of the claims 10 to 13, wherein the group -(CH2)1- located at
the I-position of the benzene ring in the formula (1').
16.The ester compound, or a pharmaceutically acceptable salt as claimed
in any of ....
the claims 10 to 15, wherein R8 and R9 are each independently -CON (R33)
(R19) - in which R18 and R19 each has the same meaning as defined above.
17. The ester compound, or a pharmaceutically acceptable salt according to any of
the claims 10 to 15, wherein R8 and R9 are each independently -COO (R20) - in
which R20 has the same meaning as defined above.
18. The ester compound, or a pharmaceutically acceptable salt according to any of
the claims 12 to 17, wherein the ring C is C6-C14 aryl.
19. The ester compound, or a pharmaceutically acceptable salt according to claim
18, wherein C6-C14 aryl is phenyl
20. The ester compound, or a pharmaceutically acceptable salt according to any of
the claims 12 to 17, wherein the ring C is C3-C7 cycloalkyL
21. The ester compound, or a pharmaceutically acceptable salt according to any of
the claims 12 to 17, wherein the ring C is

22. The ester compound, or a pharmaceutically acceptable salt according to claim 1
which is selected from the group consisting of {4-[(4'-trifluoromethyl-bipheflyl-
2-carbonyl)-amino]-pheny 1}-acetic acid 2, 2 -bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
2-phenyl-2-{2-[4-(4' -trifluoromethyl-biphenyl -2-
earbanyloxy) -phertyl] - acetoxymethyl} - malonic acid die£hylester
2-(2-{3-methyl - 4 - [ (4' - trifturomethyl-biphettyl - 2 - carbonyl) -
amino] -phenyl} - acetoxymethyl) - 2 -phenyl - malonic acid diethyl ester,
2-{2-{4- [methyl - (4' - irifluromethyl-biphenyl - 2 - earbonyl) -
amino] -phenyl} - acetoxymethyl) - 2 -phenyl - malonic acid diethyl ester,
{3 - ethyl - 4 - f (4' - trifturomethyl-biphenyl - 2 - earbonyl) - amino]
-phenyl} - acetic acid 2, 2 -bis - ethylcarbamoyl- 2 -phenyl-ethyl ester,
{4 - [ (4' - ttifluromethyl-biphenyl - 2 - carbonyl) - amino] - phenyl}
- acetic acid 9 - (2, 2, 2-trifluoro-ethykarbamoyl) - 9H - fluoren - 9 -
ylmethyl ester,
2 - { 4 - [ (4' - ttifluromethyl-biphenyl - 2 - carbonyl) - amino] -
phenyl} - propionic acid 9 - (2, 2, 2-triftuoro-ethylcarbamoyl) - 9H - fluoren
- 9 - ylmethyl ester,
2 - phenyl - 2 - (2 - { 4 - [ (4' - trifluromethyl-biphenyl- 2 - carbonyJ)
- amino] - phenyl} - acetoxymethyl) - malonic acid diethyi ester,
{4 - [ (4' - trifluromethyl-biphenyl - 2 - carbonyl) - amino] - phenyl}
- acetic acid 1 - (2, 2, 2-trifluoro-ethylcarbamoyI) cyclopentylmethyl ester,
2 - phenyl - 2 - (2 - { 4 - [ (4' - trifluromethyi-biphenyl - 2 - carbonyl)
- amino] - phenyl} - acetoxymethyl) - malonic acid diisopropyl ester,
{4 - [ (4' - trifluromethyi-biphenyl - 2 - carbonyl) - amino] - phenyl}
- acetic acid 2- phenyl - 2, 2 - bis - (2, 2, 2 - trifluoro-ethylcarbamoyl) -
ethyl ester,
2 - phenyl - 2 - (2 - { 4 - [ (4' - trifluromethyi-biphenyl - 2 - carbonyl)
- amino] - phenyl} - acetoxymethyl) - malonic acid dimethyl ester,
2- cyclopentyl- 2 - (2 - {4 - I (4' - trifluxomethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 1-( 2 , 2 ,2-trif luoro-ethylcarbamoyl)-
cyclohexylmethyl ester,
2-phenyl-2-{2-[4-(2-trifluoromethyl-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4-(2-phenoxy-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2-butoxy-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-{2-[4-(2-trifluoromethyl-benzoyloxy)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4-(2-benzoyl-benzoyloxy)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2-benzoyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dicyclohexyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-bipheny1-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-phenyl
ester,
2-butoxy-benzoic acid 4-[2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-phenyl
ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
[4-(2-phenoxy-benzoylamino)-phenyl]-acetic acid 2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-propylcarbamoyl-ethyl
ester,
{4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
2-pyridin-2-yl-2-(2-{4-[ (41 -trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-pyridin-3-yl-2-(2-{4-[ (4 ' -trif luorome thyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl) -phenyl
ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-
trifluoromethy1-biphenyl- 2 -carbonyl)- amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
[4-(2-butoxy-benzoylamino)-phenyl]-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
2-(2-{4-[(9-oxo-9h-fluorene-1-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(9h-fluorene-1-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
[4-(2-phenoxy-benzoylamino)-phenyl]-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
[4-(2-butoxy-benzoylamino)-phenyl]-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-(2-{4-[2-(4-fluoro-benzoyl)-benzoylamino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis -ethylcarbamoyl-2 -phenyl-ethoxycarbonylmethyl) - 2 -chloro-
phenyl ester,
2-phenyl-2-{2-t 4-(2-thiophen-3-yl-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-(2-{4-[(biphenyl-3-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2-[4-(2-isopropyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-{2- [ 4- (2-benzyl-benzoylamino.) -phenyl] -
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
2-phenyl-2-{2-[4-(2-trifluoromethoxy-benzoylamino)-
phenyl]-acetoxymethyl}-malonic acid diethyl ester,
2-{2-[4- (2-butoxycarbonyl-benzoylamino) -phenyl] -
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
{4-t(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2 , 2-bis-isobutylcarbamoyl-2-phenyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl)-2-
phenyl-ethyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester.
[4-(2-cyclohexyl-benzoylamino)-phenyl]-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2 , 2-bis-(2-methoxy-ethylcarbamoyl)-2-
phenyl-ethyl ester,
2-[2-(4-{[2-methyl-4-(4-trifluoromethyl-phenyl)-
thiazole-5-carbonyl]-amino}-phenyl)-acetoxymethyl]-2-
phenyl-malonic acid diethyl ester,
(4-{[2-methyl-4-(4-trifluoromethyl-phenyl)-thiazole-
5-carbonyl] -amino}-phenyl)-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
(4-{[2-(4-trifluoromethyl-phenyl)-pyridine-3-
carbonyl]-amino}-phenyl)-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
(3-methyl-4-{[2-(4-trifluoromethyl-phenyl)-pyridine-
3-carbonyl]-amino}-phenyl)-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-

3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid A,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-

ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-
malonic acid diethyl ester,
{3-(isopropyl-methyl-carbamoyl)-4-[(4'-
trif luorome thyl-biphenyl-2-carbonyl) -amino] -phenyl}-acetic
acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-(ethyl-methyl-carbamoyl) - 4 - [ (4 ' -
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-(ethyl-methyl-carbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methyl-carbamoyl)-4 -{(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-l-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2.- (2-{3-(propyl-me thyl-carbamoyl) -4- L(4 ' -trif luorome
thyl-biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-p
henyl-malonic acid diethyl ester,
{3-(methyl-propyl-carbamoyl)-4-[(4'-trifluoromethyl-
benzoyiamino ) - phenyl ] - acetoxymethyl } - 2- phenyl - malonic acid
cliethyl ester,
2 - [ 2 - (2 - { 3 - dimethykatbamoyl - 4 - [ (4' - trifluromethyl-
biphenyl - 2 - caibonyJ) - amino] - phenyl) - acetoxy ) - ethyl ] - 2 - phenyl
- maonic acid diethyl ester,
2 - (2 - [ 3 - dimethylcaibamoyl - 4 - [ ( 4' - fluoro - biphenyl - 2 -
carbonyl) - amino J - phenyl} - acetoxymethyl) - 2 - phenyl - maionic acid
diethyl ester,
2 - ( 2 - { 4- {(4' - bromo - biphenyl - 2- carbonyl) - amino ] - 3 -
dimethylcarbamoyl - phenyl } - acetoxymethyl) - 2 - phenyl - malonic acid
diethyl ester,
[ 4 - (2 - benzoyl - benzoyiamino) - 3 - dimethylcarbamoyl - phenyl
1 - acetic acid 2, 2 - bis - ethylcarbamoyl - 2 - phenyl - ethyl ester,
2-{2-[4-(2- benzoyl - benzoyiamino) - 3 - dimethylcarbamoyl
- phenyl ] - acetoxymethyl} - 2 - phenyl - maionic acid diethyl ester,
2 - ( 2 - { 3 - dimethylcarbamoyl - 4 - [ (4' - trifluromethyl-biphenyl-
2 - carbonyl) - amino] - phenyl} acetoxymethyl) - 2 -phenyl- maionic acid
dimethyl ester,
2- cyclopentyl - 2 - (2 - { 3 - dimethylcarbamoyl - 4 - [ ( 4' -
trifluromethyl-biphenyl - 2 - cafbonyl) - amino] - phenyl} acetoxymethyl) -
maionic acid diethyl ester,
2- cyclohexyl - 2 - (2 - { 3 - dimethylcarbamoyl - 4 - [ ( 4' -
trifluromethyl-biphenyl - 2 - carbonyl) - amino] - phenyl} acetoxymethyl) -
maionic acid diethyl ester,
2-(2- {4-[(4'- chloro - biphenyl - 2 carbonyl) - amino ] - 3 -
dimethylcarbamoyl - phenyl} acetoxymethyl) - 2 - phenyl - maionic acid
diethyl ester,
2-(2-(4-[(4'- acetyl - biphenyl - 2 carbonyl) - amino ] - 3 -
dimethylcarbamoyl - phenyl} acetoxymethyl) - 2 - phenyl - maionic
acid dietliyl ester,
[3 - dimethylcarbamoyl - 4 - (2 2 - phenoxy - benzoylamino ) -
phenyl ] - acetic acid 2, 2 - bis - ethykarbamoyl - 2 - phenyl -ethyl ester
2 - { 2, [3 - dimethylcarbamoyl - 4 - (2 2 - phenoxy - benzoylamino
) - phenyl ] - acetoxymethyl } - 2 - phenyl - malonic acid diethyl ester,
2 - ( 2 - {4 - [ (4' cyano - biphenyl - 2 - carbonyl) - amino ] - 3 -
dimethylcarbamoyl - phenyl} - acetoxymethyl) - 2 - phenyl - malonic acid
diethyl ester,
2 - ( 2 - {3 - dimethylcarbamoyl - 4 - [ ( 4 - methyl - 4' -
trifluoromethyl - biphenyl - 2 - carbonyl ) - amino ] - phenyl \ -
acetoxymethyl) - 2 - phenyl - malonic acid diethyl ester,
2 - ( 2 - {3 - dimethylcarbamoyl - 4 - [ ( 5 - methyl - 4' -
trifluoromethyl - biphenyl - 2 - carbonyl ) - amino ] - phenyl } -
acetoxymethyl) - 2 - phenyl- malonic acid diethyl ester,
2-[3-(2-{3- dimethylcarbamoyl - 4 - [ ( 4' - trifluromethyl-
biphenyl - 2 - carbonyl) - amino] - phenyl} - acetoxy ) - propyl ] - 2 -
phenyl - malonic acid diethyl ester,
2 - ( 2 - {3 - dimethylcarbamoyl - 4 - [ ( 5 - methoxy - 4' -
trifluoromethyl - biphenyl - 2 - carbonyl ) - amino ] - phenyl } -
acetoxymethyl) - 2 - phenyl - malonic acid diethyl ester,
2-(2-$4-[(5- chloro - 4' - trifluromethyl-biphenyl - 2 -
carbonyl) - amino] - 3 - dimethylcarbamoyl - phenyl} - acetoxymethyl) - -
phenyl - malonic acid diethyl ester,
2 - ( 2 - {3 - dimethylcarbamoyl - 4 - [ ( 6 - methyl - 4' -
trifluoromethyl - biphenyl - 2 - carbonyl ) - amino ] - phenyl } -
acetoxymethyl) - 2 - phenyl - malonic acid diethyl ester),
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -aminoj -phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino ] -phenyl} -acetoxymethyl) - 2 -p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4 -[(4'
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-[(41-
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(4 -chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4 f-trifluoromethyl-
biphenyl - 2 - carbonyl) - amino ] -phenyl} - acetoxymethyl) - 2 -
phenyl-succinic acid diethyl ester,
2- ( 2-{3-dimethylcarbamoyl-4-[(4•-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino ] -phenyl} - acetoxymethyl) - 2 - ( 2 -
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) - 2 - (3 -
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino ] - 3 -dimethylcarbamoyl-phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxy)-ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4l-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}-2-phenyl-malonic
acid diethyl ester,
2 - (2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl) - amino ] - phenyl} - acetoxymethyl) - 2 -phenyl -malonic
acid diethyl ester,
2-ethyl-4-trifluoromethyl-benzoylamino)-phenyl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3-acetoxy-2-
acetoxymethyl-2-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[ (4 ' -trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiophen-2-yl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[ (4 ' -trif luorome thyl-
biphenyl - 2 - carbonyl) - amino ] -phenyl} - acetoxymethyl) - 2 -
thiophen-3-yl-malonic acid diethyl ester,
2- ( 2- {4-dime thylcarbamoyl -5- [ (4 ' -trif luorome thyl-
biphenyl-2-carbonyl) -amino] -pyridin-2-yl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- [ (4 ' - trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2- (3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[ (4 ' -trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3- dime thylcarbamoyl - 4 - [ (4 ' - trif luorome thyl -
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiazol-2-yl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- [ (4 ' -trif luoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) - 2 -
isopropyl-malonic acid diethyl ester,
2-sec-butyl-2- (2-{3-dimethylcarbamoyl-4- [ (4 ' -
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
isobutyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[ (4 ' -trif luoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
propyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-ethyl-
malonic acid diethyl ester,
2-butyl-2-(2-{3-dimethylcarbamoyl-4-[ (4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-allyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-2,2-bis-
ethoxycarbonyl-propionic acid ethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(1-
methyl-butyl)-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid.2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4 -(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 2, 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-f(4'-
trifluoromethyl-biphenyl- 2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-bipheny
1-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{3-[(41-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-phenyl-
propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl) -amino] -phenyl}-acetic acid 3 , 3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -aminoj -phenyl}-acetic acid 4 , 4-bis-ethylcarbamoyl-
4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-aminoJ-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2-f2-(2-{2 -methoxy- 3 - [ (4 ' - trif luorome thyl - biphenyl - 2 -
carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-malonic
acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 3 , 3-bis-ethylcarbamoyl-
3-phenyl-propyl ester,
2- [2- (2-{2-ethoxy-3- [ ( 4 ' -trif luoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-malonic
acid diethyl ester,
2- [2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-
phenyl-malonic acid diethyl ester,
2- [2-(2-{2-methoxycarbonyl-3-[ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxy) -ethylJ -2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[ (4 ' -trif luoromethyl-
biphenyl-2-carbonyl) -aminoj -phenyl}-acetoxy) -ethyl J -2-
phenyl-malonic acid diethyl ester,
4- [ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -
benzoic acid 2-[9-(2,2,2-trifluoro-ethylcarbamoyl)-9h-
fluoren-9-yl]-ethyl ester,
n-biphenyl-2-yl-terephthalamic acid 2-[9-(2-2,2-
trif luoro-ethylcarbamoyl) -9h-f luoren-9-yl ] -ethyl ester.
4 - [ (4' - irifiuoromethyi - biphenyl - 2 - carbonyl) - amino j -
benzoic acid 3, 3 - diphenyl - 3 - ( 2, 2, 2 - trifluro - ethylcarbamoyl) -
propyl ester,
2 - pheny - 2- ( 2 - {4 - [ ( 4' - triftuoromethyl - biphenyl - 2 -
carbonyl) - amino ] - benzoyloxy - emyl) - maionic acid diethyi ester,
2 - ( 2 - {3 - methyl - 4 - [ ( 4' - triftuoromethyl - biphenyl - 2 -
carbonyl) - amino ] - benzoyloxy - ethyl) - 2 - phenyl - maionic acid
diethyi ester,
2 - ( 2 - {2 - chloro - 4 - {( 4' - triftuoromethyl - biphenyl - 2 -
carbonyl) - amino ] - benzoyloxy - ethyl) 2 - phenyl - maionic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
2-{2-[4-(2-benzoyl-benzoyloxy)-benzoyloxy]-ethyl}-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2-
chloro-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(3,3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4- ( 3 , 3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-
dichloro-phenyl ester,
4-methyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-cyclohexanecarboxylic acid 2-[9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
cyclohexanecarboxylic acid 2-[9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-yl]-ethyl ester,
2-phenyl-2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-cyclohexanecarbonyloxymethyl}-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-cyclohexanecarbonyloxy}-ethyl)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4f-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-piperidin-l-yl}-acetoxymethyl)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-indol-1-yl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbony1)-aminoj-benzoimidazol-1-yl}-acetoxymethyl)-2 -
phenyl-malonic acid diethyl ester,
[2-oxo-3-(4'-trifluoromethyl-biphenyl-2-carbonyl)-
2,3-dihydro-benzooxazol-6-yl]-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -aminoj-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-propionyloxymethyl)-2-
phenyl-malonic acid diethyl ester,
4-{[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
methyl}-benzoic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
5-(2,2-bis-ethylcarbanioyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl~
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoimidazol-1-yl}-acetoxymethyl)-malonic
acid diethyl ester,
3-{[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
methyl}-benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-

benzoic acid methyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphfenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester.
2-[2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[2-OXO-3-(4'-trifluoromethyl-biphenyl-
2-carbonyl) -2 , 3-dihydra-benzooxazol-6-yl ] -acetoxymethyl}-2
phenyl-malonic acid diethyl ester,
2-{2-[8-oxo-7-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-7-aza-bicYclo(4.2.0Jocta'l(6), 2,4-trien-3-yl]-
acetoxymethyl}-2-phenyl-malonic acid diethyl ester,
2-(2-(3-isopropoxycarbonyl-4-[(4'-trifluorometbyl-
biphenyl-2-earbonyl}-amino]-phenyl)-acetpxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-l2-{3-metboxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-earbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(3-dimethylcarbamoyl-4-{[l-(2-nitrol-4-trifluoro-
methyl-phenyl)-pyrrolidine-2-earbonyl]-amino}-pnenyl)-
acetoxcymettiyl}-2-phenyl-malonic acid dietpyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl)-acetoxymethyl)-2-pbenyl-inalonic
acid diethyl ester,
2-(2-{3-methoxyearbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-
malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4-
trifluoromethyl-biphenyl-2-earbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
earbonyl)-amino]-biphenyl-3-yl}-acetoxymethyl)-malonic acid
diethyl ester.
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phanyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(methoxy-methyl-carbamoyl)-4-[(4 ' -
trif luorome thyl-biphenyl- 2 -carbonyl) -amino ] - phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-me thyl-propyl) - 4 - [ ( 4 ' -
trifluoromethy1-biphenyl- 2 -carbonyl) -amino] -phenyl} -acetoxym
ethyl)-2-phenyl-malonic acid diethyl ester.
23. The ester compound ,or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
2-phenyl-2-{2- [4-[ (4 ' - trif luorome thyl-biphenyl-
2-carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[ (4 ' -trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2- (2-{4-[methyl-(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl) -
amino]-phenyl}-acetic acid 2,2-bis- ethylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 9- ( 2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-ylmethyl ester,
{ 4 - [(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-propionic acid 9-(2,2,2-trifluoro-
ethylcarbamoyl)-9h-fluoren-9-ylmethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[4'-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino ] -phenyl} -acetoxymethyl) -malonic acid diethyl
ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
diisopropyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[ (4' -trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dicyclohexyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-
ethyl ester,
{4-[ (4 ' -trif luoromethyl-biphenyl- 2 -carbonyl) -amino] -
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl-2-phenyl-malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2,2-trifluoro-ethylcarbamoyl)-ethoxycarbonylmethyl]-
phenyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-
ethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl-malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-phenyl
ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-trifluoro-
me thyl -biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}- acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4 -[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl}-amino]-
phenyl}- acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4- [ (biphenyl-2-carbonyl) -amino] -phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis -ethylcarbamoyl-2 -phenyl-ethoxycarbonylmethyl) - 2 -
chloro-phenyl ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-
biphenyl - 2 - carbonyl} - amino ] -phenyl} -ace toxyme thyl) - 2 -
phenyl-malonic acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino ] -phenyl} -acetoxymethyl) -malonic acid
diisobutyl ester,
{ 4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl-2-
phenyl-ethyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-{ethylcarbamoyl-2-phenyl-ethyl ester,
{4- [ (3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl}-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl}-
amino]-phenyl}-acetic acid 2,2-bis-(2-methoxy-
ethylcarbamoyl)-2-phenyl-ethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl}-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl}-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isopropyl-4-f(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2 -{3 -dimethylcarbamoyl-4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-t(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-ethyl ester,
2-(2 -{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl} -acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 4,4'-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2
-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-f(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl- 4 -[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-(isopropyl-methylcarbamoyl)-4-[(4 '-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-
bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-(ethyl-methylcarbainoyl) -4- [ (4 ' -trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2 -phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-1(4'-trifluoromethy1-
biphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrrolidine-1-carbonyl)-4 -[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-l-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl) -melonic acid diethyl ester.
2 - [ 2 - ( 2 - 13 - dimethylcarbamoyl - 4 - [ (4' - trifluoromethyl -
biphenyl - 2 - carbonyl ) - aniino ] - phenyl } - acetoxy) - ethyl ] - 2 -
phenyl - malonie acid diethyi ester,
2 - ( 2 - {3 - dimeiftylcarbamoyl - 4 - [ (4' - fluoro - biphenyl- 2 -
carbonyl) - aniino ] - phenyl} - acetoxymethyl) - 2 - phenyl malonic acid
diethyl ester,
2-(2-{4-[(4'- bromo -biphenyl- 2 - carbonyl) - amino ] - 3 -
dimethylcafbajmoyl - phenyl} - acetoxymethyl) - 2 - phenyl - maionic acid
diethyi ester,
2 - ( 2 - 13 - dimethylcarbamoyl - 4 - [ (4' - trifluoromethyl -
biphenyl - 2 - carbonyl) - amino ] - phenyl } - acetoxymethyl) - 2 - phenyl
- malonic acid dimethyl ester,
2 - cyclopentyl - 2 - ( 2 - { 3- dimethylcarbamoyl - 4 - [ (4' -
trifluoromethyl - biphenyl - 2 - carbonyl) - amino ] - phenyl} -
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[ ( 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl}-amino] - 3 -
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2 -carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
t rifluoromethyl-biphenyl-2-carbonyl)- amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2- [3-(2-{3-dimethylcarbamoyl-4-[(4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-t(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[ (4'-
trifluorome thyl- biphenyl -2- carbonyl) - amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[ (4'-
trif luorome thyl-biphenyl- 2 -carbonyl) -amino ] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-(3'-chloro-4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
(5-nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-4-
[ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4- [ ( 4'-
t rifluoromethyl-biphenyl- 2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3 -dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4 -
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
(2-methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
(3-methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)- amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl}-malonic acid diethyl ester,
2-(2-{4-(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-araino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2-{3-dimethylcarbamoyl-4 -[(6-fluoro- 4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4 -[(5-methyl-
4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-1(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-
4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4'-bis-4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-ethyl-4-
trifluoromethyl-benzoylamino)-phenyl]-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(4'-ethyl-bipheny1- 2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-f(4'-trifluoromethyl-
biphenyl-2-carbonyloxy)-phenyl]-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-hydroxy-
2-hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-acetoxy-
2-acetoxymethyl-2-phenyl-propyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
{ 3 -hydroxy- 4 - [ ( 4 ' - trif luorome thyl - biphenyl - 2 -
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl- 2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl- 2-phenyl-ethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-ace toxyme thyl) -2-phenyl-malonic
acid diethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4- [ (4 ' - trif luorome thyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid
3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
{ 3 -ethoxy-4- [ (4 ' - trifluoromethyl-biphenyl - 2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{ 3 -ethoxy- 4 - [ (4 ' - trif luorome thyl - biphenyl - 2 -
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4- [ (4 ' -trif luorome thyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl- 2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl- 2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, s
2-{2-[3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4 -[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-
trifluoromethyl- biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl~4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2 -
phenyl-malonic acid diethyl ester,
(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl- 2-carbonyl)-aminoJ-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-f(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) - 2 -
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-
propyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3.3-bis- propylcarbamoyl-
propyl ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy-ethyl)-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{3 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-
phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-aminoJ-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-methoxy-3-[(4 ' -trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2 -[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[9-(2,2,2 -trifluoro-ethylcarbamoyl)-9h-
fluoren-9-yl]-ethyl ester.
n-biphenyl - 2 - yl - terephthalmic acid 2 - { 9 - (2, 2, 2 - trifluoro-
ethylcarbamoyl) - 9h - fluorn - 9 - yl ] estex,
4 - [ (4' - trifiuoromethyl - biphenyl - 2 - earbonyl ) - amino ] -
benzoic acid 3, 3 - diphenyl - 3 - ( 2, 2, 2 - ttifluoro-ethyicarbamoyl) -
propyl ester,
2 - phenyl - 2 - ( 2 - { 4 - [ (4' - trifluoromethyl - biphenyl - 2 -
catbonyl) - amino ] - benzoyloxy } - ethyl) - malonic acid diethyl ester,
2 - ( 2 - { - methyl - 4 - [ ( 41 - trifluoromethyl - biphenyl - 2 -
carbonyl) - amino ] - benzoyloxy } - ethyl) - 2 - phenyl - malonic acid
diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbony)-2 -chloro-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-2,6-dichloro-
phenyl ester,
2-(2-{3-ethoxycarbonyl-4-f(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-propionyloxymethyl)-2-
phenyl-malonic acid diethyl ester,
5-(2,2-bis-ethylcarbamoyl- 2-phenyl-ethoxycarbonyl-
methyl)-2-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzole acid benzyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid ethyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid methyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2 - (2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2 - (2-{3-acetylamino-4-[(4'-trifluoromethyl-biphenyl-
2 -carbonyl) -amino] -phenyl} -acetoxymethyl) - 2 -phenyl-malonic
acid diethyl ester,
2- (2-{3-methoxycarbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4'-
tr if luorome thyl - biphenyl - 2 - carbonyl) - amino ] - phenyl} -
acetqxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -phenyl -2-(2-{6-[(4r- trif luorome thyl - biphenyl - 2 -
carbonyl) -amino] -biphenyl-3-yl}-acetoxymethyl) -malonic acid
diethyl ester,
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl - 2 - carbonyl) - amino ] -phenyl} - 3 - ace t oxyme thyl) - 2 -
phenyl-malonic acid diethyl ester,
2 - (2-{3-methoxy-methylcarbamoyl)- 4-[(4 ' -
trifluorome thyl - biphenyl - 2 - carbonyl) - amino ] - phenyl} - 3 -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-3-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-1(4'-
trifluoromethyl-biphenyl-2-carbonyl)-araino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
24. The ester compound ,or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl)-2-phenyl-
ethyl ester,
2-phenyl-2-{2-[4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4 -[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[methyl-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-2-phenyl]-acetic acid 2,2-bis-
ethylcarbamoyl -phenyl -ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic acid
diisopropyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-
trifluoro-ethylcarbamoyl)-ethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4 ' -trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dicyclohexyl ester,
{4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-
phenyl ethyl ester,
{ 4- [ ( 4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2 , 2-bis-phenylcarbamoyl-ethyl
ester,
{4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl) -amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-phenyl-
ethyl ester,
2-benzyl-2-(2-{4-[(4' -trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-(2-{2-methyl-4-[(4 ' -trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2 , 2-bis- ( 2 , 2 ,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2,2-1rifluoro-ethylcarbamoyl) - ethoxycarbonylmethyl ] -
phenyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
diethyl ester,
{4-[ (biphenyl-2-carbonyl) -amino] -phenyl}-acetic acid
2-phenyl-2 , 2-bis- (2, 2 , 2-trif luoro-ethylcarbamoyl) -ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4 - [ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-
ethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -malonic
acid diethyl ester,
4'-trifluoromethyl-biphenyl-2-carbxylic acid
4-(2,2-bis-ethylcarbamoyl)-2-phenyl-ethoxycarbonylmethyl}-
phenyl ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid
4-(2,2-bis-ethylcarbamoyl)-2-phenyl-ethoxycarbonylmethyl)-
2-chloro-phenyl ester,
2-(2-{4-fisopropyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-(3-methyl-
butylcarbamoyl)-2-phenyl-ethyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{4-[(4'-chloro-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
{4-[(3'4'-dichloro-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-
ethyl ester,
{3-methyl-4-[ (4 ' - trif luoromethyl -biphenyl -,2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-2-
phenyl-ethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3- brorao-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dxmethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-biphen
yl-2-carbonyl)-aminoJ-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
{3-(isopropyl-methylcarbamoyl)-4-[(4'-trifluoromethyl
-biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4- [ (4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3- (methyl-propylcarbamoyl) -4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetic acid
2-ethylcarbanioyl-2rphenyl-ethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-carbonyl)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-carbonyl)-4-[(4 ' -
trif luoromethyl-biphenyl-2-carbonyl) -amino ] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2-
propionylamino-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(2,5-
dioxo-pyrrolidin-1-yl)-2-phenyl-ethyl ester,
{ 3 - dime thylcarbamoyl - 4 - [ (4 ' - trif luorome thyl -
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-ethylcarbamoyl-benzyl ester,
{3 -dimethylcarbamoyl-4-[(4'-trifluoromethy 1 -
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-ethylcarbamoylmethyl-benzyl ester,
{3-dime thylcarbamoyl-4- [ (4 ' -trif luorome thyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-isopropylamino-2-phenyl-ethyl ester hydrochloride.
2-[2-(2-{3-dimethylcarbamoyl-4-[ (4 '-trif luorome thyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy) -ethyl] -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4- [ ( 4'-fluoro-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-dimethylcarbajnoyl-4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-acethylamino-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-aminoJ-phenyl}-acetic acid
2-butyrylamino-2-phenyl-ethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid dimethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
trifluromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-methanesulfonylamino-2-phenyl-ethyl ester,
3-(2-{3-dimethylcarbamoyl-4-[ (4 ' -trifluoromethyl-
biphenyl - 2 - carbonyl) - amino ] -phenyl} - acetoxy) - 2 - phenyl -
propionic acid ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-(methyl-
propionyl-amino)-2-phenyl-ethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluromethyl-
-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trif luromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trifluorome thyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2 -(2 -{3-dimethylcarbamoyl-4-[(3'-fluoro- 4 " -
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-f(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2 -(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro- 4 - [ (4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro-4- [ (4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-m-
tolyl-malonic acid diethyl ester,
2 -(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[ (4 '-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2 -(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl)-amino]-phenyl}-acetoxymethyl) - 2 -
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-(2-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl- 4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl--malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4 ' -
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl) -amino] -phenyl} -acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4 -[(2-e thyl-4-
trif luoromethyl-benzoylamino) -phenyl] -acetoxymethyl}-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl) -amino]-phenyl}-ace toxyme thyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyloxy)-phenyl]-acetoxymethy1}-2 -
phenyl-malonic acid diethyl ester,
{3-dimethylcarbamoyl-4- f (4 ' -trif luoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-ethyl-
2-phenyl-butyl ester,
{3-dime thylcarbamoyl-4- f (4 ' -trif luoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 1-phenyl-
cyclopropylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-
diphenyl-ethyl ester,
{3~dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid l-phenyl~
cyclopentylmethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethy1-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3-hydroxy-
2-hydroxymethyl-2-phenyl-propyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
3-acetoxymethyl-2-phenyl-propyl ester,
2-(2 -{3-dimethylcarbamoyl-4-[(4'-1rifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl]-2-
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl]-2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -pyridin-2-yl}-acetoxymethyl) -
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl] -2- ( 3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2- ( 5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
{3-hydroxy-4- [ (4 ' - trif luorome thyl-biphehyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester
{3-me thoxy-4- [ (4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester
2- ( 2-{3-methoxy-4- [ ( 4 ' -trif luoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl} -acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)- amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
{3-dimethylamino-4-[(4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4 ' -trifluoromethyl-biphenyl-
2- carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)- malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)- malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-f(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl -2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-
propyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-
propyl ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis~isopropylcarbamoyl-3-
phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 4,4-bis -
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[(biphenyl-2-carbonyl)-amino]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-(2-biphenyl-2-yl-acetylamino)-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-naphthalen-1-yl-3-(2,2,2-
trifluoroethylcarbamoyl)-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-[2-(2,2,2-trifluoro-
ethylcarbamoyl) -naphthalen-1-yl]-propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3,3-diphenyl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-phenyl-3-(2,2.2-trifluoro-
ethylcarbamoyl ) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 2-[8-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-ethyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-(2,6-dichloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl ) -propyl ester,
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzoic acid 3-(2-chloro-phenyl)-3-(2,2,2-trifluoro-
ethylcarbamoyl) -propyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2 -(2-{2-chloro-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino] -benzoyloxy}-ethyl) -2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-benzoyloxy]-ethyl}-malonic acid diethyl ester,
4- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl)-amino]-
benzole acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis - e thylcarbamoyl - 3 -phenyl -propoxycarbonyl) - 2 - chloro -
phenyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid
4- (3 , 3-bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl) -phenyl
ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl) -2,6-dichloro-p
henyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-propionyloxymethyl) -
2-phenyl-malonic acid diethyl ester,
3-{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino] -phenyl} -propionic acid e thylcarbamoyl -phenyl -
methyl ester,
5- (2, 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2-4- [ (4 ' -trif luoromethyl-biphenyl- 2 -carbonyl) -
amino]-benzoic acid benzyl ester,
5- ( 2 , 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-f(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid ethyl ester,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzole acid methyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-aminoJ-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4f-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- 2-phenyl-malonic acid diethyl ester,
2-phenyl-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -biphenyl-3-yl}-acetoxymethyl) - malonic acid
diethyl ester,
2-(2-{3-formyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester.
2 - ( 2 - { 3 - (methoxy-methylcarbamoyl) - 4 - [ ( 4 ' -
trif luoromethyl-biphe:nyl-2-carbonyl) -antino] -phenyl} -
acetoxymethyl) -2-phenyl-raalonic acid diethyl ester,
2-(2-{3-isobutyryl-4-[ (41 - trif luorome thy 1-biphenyl-
2-carbonyl) -amino] -phenyl}-ace toxymethyl) -2-phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l -hydroxy- 2-methyl-propyl) - 4 - [ ( 4 ' -
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -
acetoxymethyl) -2-phenyl-malonic acid diethyl ester.
25. The ester compound , or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
{4-[ (4 '-trifluoromethyl-biphenyl-2-carbonyl) -amino]-
phenyl}-acetic acid 2.2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-ethyl-4- [ (4 ' -trif luoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{4- [ (4' -trifluoromethyl-biphenyl-2-carbonyl) -amino] -
phenyl}-acetic acid 2-phenyl-2,2-bis-(2 , 2 , 2-trif luoro-
ethylcarbamoyl)-ethyl ester,
{4- [ ( 4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -
phenyl}-acetic acid 2 , 2-bis-cyclohexylcarbamoyl-2-
phenyl-ethyl ester,
{4- [ ( 4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -
phenyl}-acetic acid 2-phenyl-2 , 2-bis-phenylcarbamoyl-
ethyl ester,
{4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl) -amino]-
phenyl}-acetic acid 2 , 2-bis-isopropylcaramoyl-2-phenyl-
ethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl ] -phenyl ester,
biphenyl-2-carboxylic acid 4 - f 2-phenyl-2 , 2-bis-
(2 2 , 2-trif luoro-ethylcarbamoyl) -ethoxycarbonylmethyl ] -
phenyl ester,
{4- [(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)- ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl- 4 - [ (4 ' -
trifluoromethyl-bipheny1-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
{4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl) -phenyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis- butylcarbamoyl-2-phenyl-ethyl-
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-propyl
ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl ethyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4 - (2 , 2 -
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl)-2-chloro-
phenyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2 , 2-bis-(3-methyl-butylcarbamoyl)-2 -
phenyl ethyl ester.
{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl ethyl ester,
{4 -[(3',4'-dichloro-biphenyl-2 -carbonyl)-amino J-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl)-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl)-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-
2-phenyl-ethyl ester,
{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl -phenyl -ethyl ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic . acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl -2 -phenyl -ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{3-methylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl -2 -phenyl -ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl -2 -phenyl -ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl- 4 - [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(isopropyl-methylcarbamoyl) - 4 - [ ( 4 ' -
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-acetic
acid 2,2-bis- ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
e thylcarbamoy1-3-phenyl-propy1 ester,
{3-(piperidin-l-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidin-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis -
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoy1-3-phenyl-propyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-aminoj-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-aminoj-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylamino-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl
ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propylcarbamoyl-
propyl ester,
{3-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-isopropylcarbamoyl-3-phenyl-
propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis -
ethylcarbamoyl-3-phenyl-propyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 3-phenyl-3,3-bis-
propylcarbamoyl-propyl ester,
{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]- phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
4 -[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino ] -
benzoic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl) -2-chloro-
phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl)-phenyl ester,
4'-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl) -2,6-dichloro-
phenyl ester,
5-(2,2-bis- ethylcarbamoyl - 2 -phenyl - e thoxycarbonyl -
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-benzoic acid benzyl ester,
5- (2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)-2-[(4'-trifluoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid,
5- (2 , 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl)- 2-[(4'-trifluoromethyl-biphenyl- 2 -carbonyl) -
amino]-benzoic acid ethyl ester, and
5- ( 2 , 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2- [ ( 4 ' -trifluoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid methyl ester.
26. The ester compound , or a pharmaceutucally acceptable
salt according to claim
1, which is selected from the group consisting of
2 -phenyl -2-{2-[4-(4'- trif luoromethyl -biphenyl - 2 -
carbonyloxy)-phenyl J-acetoxymethyl}-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) - amino J -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2- (2-{4-[methyl-(4'-trifluoromethyl-biphenyl-2- •
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-f (4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2- (2-{4- [ ( 4 ' - trif luoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
diisopropyl ester,
2-phenyl-2-(2-{4-[ (4 ' -trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dimethyl ester,
2-cyclopentyl-2- (2-{4- [ ( 4 ' -trif luoromethyl-biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl) -malonic acid
diethyl ester,
2 -phenyl -2-(2-{4-[(4'- trif luoromethyl - biphenyl - 2 -
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
dicyclohexyl ester,
2-benzyl~2-(2-{4-[ (4 ' - trif luoromethyl-biphenyl-2 -
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2- ( 2- {2-methyl-4-[(4'-trifluoromethyl-biphenyl-2 -
carbonyl) -amino ] -phenyl} -acetoxymethyl) - 2-phenyl-malonic
acid diethyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-raalonic acid
diethyl ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2- carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2-phenyl-2-(2-{3-trifluoromethyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)- malonic acid diethyl ester,
2-(2-{4-[(4'-methyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-methoxy-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(3'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-(2-{4-[isopropyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[cyclohexyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dipropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisobutyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isobutyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
{3-(pyrroldine-1-carbonyl)-4-[(4'-1rifluorome thyl -
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl-2-(2-{3-(pyrroldine-1-carbonyl)-4-[(4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl-2-(2-{3-(piperidine-1-carbonyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoy1-4 -[(4'-1rifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-aminoJ-phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-(2-{4-[(4'-chloro-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-
3-dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-
3-dimethylcarbamoyl-phenyl}-acetoxymethyl)-2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid di-2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4r-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)- amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl -2 -carbonyl) -amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-4-
[ ( 4 ' - trif luoromethyl - biphenyl - 2 - carbonyl) - amino ] - phenyl} -
acetoxymethyl)-malonic acid diethyl ester,
2-{2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl -2 - carbonyl) - amino ] -phenyl} -acetoxymethyl) - 2 -
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2 -fluoro-4 -
[ (4 '-trifluoromethyl-biphenyl- 2 -carbonyl) -amino] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3 -bromo-5-dimethylcarbamoyl-2-fluoro-4-
[ (4 ' -trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl} -
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[ (4 '-trif luoromethyl-
biphenyl - 2 - carbonyl) - amino ] - phenyl} - acetoxymethyl) - 2 - o -
tolyl-malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- f (4 ' - trif luoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) - 2-m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -2-p-
tolyl-malonic acid diethyl ester,
2-{3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[ (4' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl }-
acetoxymethyl)-malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2 - (4 - chloro -phenyl )-2-(2-{3- dimethylcarbamoyl - 4 -
[ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2- (2- { 3-dimethylcarbamoyl-4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2- (2-
methoxy-phenyl)-malonic acid diethyl ester,
2- ( 2- { 3-dimethylcarbamoyl-4- [ { 4 ' -trif luoromethyl-
biphenyl-2-carbonyl)-araino]-phenyl}-acetoxymethyl) - 2 - (3 -
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[ (4 '-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl)-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino)-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl7 4-[(6-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]-2-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4r-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl)-malonic acid diethyl ester,
2-[2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl]-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3-methyl-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-{2-[4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}-2-phenyl)-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-{2- [3-dimethylcarbamoyl-4- [ (2-ethyl-4-trifluoro-
methyl-benzoylamino) -phenyl] -acetoxymethyl} -2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4- [ (4 ' -ethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3- dime thylcarbamoyl - 4 - [ ( 4 ' - isopropenyl -
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2- ( 2-{3-dimethylcarbamoyl-4- [ (4 ' -isopropyl-biphenyl-
2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2 - { 2 - [ 3 - dime thylcarbamoyl - 4 - [ (4 ' -1 r if luorome thyl -
- biphenyl - 2 - carbonyloxy) -phenyl J - acetoxymethyl} - 2 -phenyl -
malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- [ (4 ' -trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiophen-2-yl- malonic acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4- [ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiophen-3-yl- malonic acid diethyl ester,
2-(2-{4- dime thylcarbamoyl - 5 - [ (4 ' - tr if luoromethyl -
biphenyl-2-carbonyl) -amino] -pyridin-2-yl}-acetoxymethyl) -
2-phenyl- malonic acid diethyl ester,
2-(2-{3- dime thylcarbamoyl - 4 - [ (4 ' - trif luorome thyl -
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2- (3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2- (2-{3-dime thylcarbamoyl-4- [ (4 ' - trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2- ( 5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2- ( 2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-aminoj-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-{2-[3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyloxy)-phenyl]-acetoxymethyl}-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid diethyl
ester,
2-phenyl-2-[2-(2-{3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-malonic acid
diethyl ester,
2-[2-(2-{4-methyl-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methyl-5-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-methoxy-3-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-
malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-3-[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-phenyl-malonic
acid diethyl ester,
2-[2-(2-{2-isopropoxy-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-methoxycarbonyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-[2-(2-{2-ethoxy-5-methyl-3-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl]-malonic acid diethyl
ester,
2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxyj-benzoyloxy}-ethyl}-malonic acid diethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl- 2 -carbonyl)-amino 3 -phenyl}-acetoxymethy1) - 2 -
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[ (4 '-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-propionyloxyinethyl) -
2-phenyl-malonic acid diethyl ester,
2-(2-{3-benzyloxycarbony-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2~{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino1 -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester.
2-(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-t(4'-trifluoromethyl-biphenyl-
2-carbonyl) -aininol -phenyl>-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-{{4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl) -amino]-phenyl}-acetoxymethyl) -
2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{6-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino] -biphenyl-3-yl}-acetoxyniethyl) -malonic acid
diethyl ester,
2-{2-{3-formy1-4-{{4'-trifluoromethyl-bipheny1-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(methoxy-methylcarbamoyl)-4-[(4'-trifluoro-
me thyl-biphenyl- 2 -carbonyl )-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-isobutyryl-4-f(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
27. The ester compound /Or a pharmaceutucally acceptable
salt according to claim
1, which is selected from the group consisting of
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoro-
ethylcarbamoyl)-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-cyclohexylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2-phenyl-2,2-bis-phenylcarbamoyl-ethyl
ester,
{4-[(A'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isopropylcarbamoyl-2-
phenyl-ethyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2-phenyl-2,2-bis-(2,2,2 -trifluoro-ethylcarbamoyl)-ethyl
ester,
2-phenyl-2-(2-{2-trifluoromethyl-4 -[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
{4 -[(4'-1rifluoromethyl-biphenyl- 2 -carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-methylcarbamoyl-2-phenyl-ethyl
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2.2-bis-butylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethyl-
carbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3,3-bis-ethylcarbamoyl-3-phenyl-propyl-
ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 3-phenyl-3,3-bis-propyl- carbamoyl-
propyl ester,
{4-[(biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid
2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-isobutylcarbamoyl-2-phenyl-
ethyl ester,
{4-t(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(3-methyl-butylcarbamoyl)-2-
phenyl-ethyl ester,
{4-[(4 ' -chloro-biphenyl-2-carbonyl)-amino]-phenyl}-
acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester,
{4-[(3',4'-dichloro-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl
ester,
{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetic acid 2,2-bis-(2-methoxy-ethylcarbamoyl)-
2-phenyl-ethyl ester.
{3-isopropyl-4 -[(4'-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino ] -phenyl}-acetic acid 2 , 2-bis-ethylcarbamoyl-
2-phenyl-ethyl ester,
{3-ethyl-4-[(4 ' -trifluoromethyl-biphenyl- 2 -
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-ethyl-
carbamoyl-3-phenyl-propyl ester,
{3-isobutyl-4-t(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-ethyl-
carbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4- [ ( 4 ' -trif luorome thyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 2-phenyl-
2,2-bis-propylcarbamoyl-ethyl ester,
{ 3 -methylcarbamoyl-4 - [ (4 ' -trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dime thylcarbamoyl-4- [ (4 ' - trif luorome thyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-benzylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 4,4-bis-
ethylcarbamoyl-4-phenyl-butyl ester,
{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(isopropyl-methylcarbamoyl-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-
amino]-phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-
phenyl-ethyl ester,
{3-(ethyl-methylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-(piperidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methyl-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(methy1-propylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,.
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2-phenyl-2,2-bis-
propylcarbamoyl-ethyl ester,
{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-ethoxy-4-[(4"-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl es ter,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 3,3-bis-
ethylcarbamoyl-3-phenyl-propyl ester,
{3-propoxy-4-[ (4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-benzyloxy-4- [ (4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-dimethylamino-4- [ (4 ' -trif luoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-piperidin-l-yl-4-[ (4 ' -trif luoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-pyrrolidin-l-yl-4- [ (4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
4- [ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -
benzoic acid 3 , 3-bis-ethylcarbamoyl-3-phenyl-propyl ester,
5- (2 , 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2-[ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid benzyl ester,
5- ( 2 , 2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2- [ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid,
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2- [ (4 ' -trif luoromethyl-biphenyl-2-carbonyl) -amino] -
benzoic acid ethyl ester, and
5-(2,2-bis-ethylcarbamoyl-2-phenyl-ethoxycarbonyl-
methyl) -2- [ (4 ' -trifluoromethyl-biphenyl-2-carbonyl) -
amino]-benzoic acid methyl ester.
28. The ester compound ,or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
2- ( 2- {3-methyl-4 -[(4'-trifluoromethyl-biphenyl-
2-carbony1)-amino]-phenyl}-acetoxymethyl)-2-phenyl-maIonic
acid diethyl ester,
2-(2-{4-[methyl-(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diisopropyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dimethyl ester,
2-cyclopentyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
dicyclohexyl ester,
2-benzyl-2-(2-{4-[(4r-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-(2-{2-methyl-4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-cyclohexyl-2-(2-{4-[(4'-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-malonic acid
diethyl ester,
2-phenyl-2-(2-{2-trifluoromethyl-4-f(4'-1rifluoro -
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
malonic acid diethyl ester,
2-pyridin-2-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2-pyridin-3-yl-2-(2-{4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)- malonic
acid diethyl ester,
2 -phenyl -2-(2-{3- trif luoromethyl - 4 - [ ( 4 ' -1 rif luoro -
methyl-biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -
malonic acid diethyl ester,
2-(2-{4-[(4' -methyl-biphenyl-2-carbonyl) -amino] -
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(4' -methoxy-biphenyl-2-carbonyl) -amino] -
phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-phenyl-2-(2-{4-[ (3'-trifluoromethyl-biphenyl-2-
carbonyl) -amino]-phenyl}-acetoxymethyl) -malonic acid diethyl
ester,
2-(2-{4-[ isopropyl - (4 ' - trif luoromethyl - biphenyl - 2 -
carbonyl) -amino]-phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[ cyclohexyl - (4 ' - trif luoromethyl - biphenyl - 2 -
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{4-[ (4 ' - trif luoromethyl-biphenyl-2-
carbonyl) -amino]-phenyl}-acetoxymethyl) -malonic acid
dipropyl ester,
2-phenyl-2-(2-{4- [ (4 ' -trif luoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -malonic acid
diisobutyl ester,
2-(2-{4-[ethyl-(4'-trifluoromethyl-biphenyl--2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-ethyl-4-(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl} -acetoxymethyl) -2 -phenyl-malonic
acid diethyl ester,
2 - (2 - { 3 - isopropyl - 4 - (4 ' - trif luoromethyl - biphenyl - 2 -
carbonyl) -amino]-phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2 - ( 2 - { 3 -isobutyl- 4 - ( 4 ' - trif luoromethyl - biphenyl - 2 -
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2- (2-{3-chloro-4-(4 ' -trif luoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)- 2-phenyl-malonic
acid diethyl ester,
2-(2-{3-bromo-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diisopropylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2
-phenyl-malonic acid diethyl ester,
{3-(ethyl-methylcarbamoyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
{3-(pyrrolidine-1-carbonyl)-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester,
2-phenyl~2-(2-{3-(pyxrolidine-l-carbonyl)-4-[(4' -
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl }-
acetoxymethyl)-malonic acid diethyl ester,
2-phenyl~2-(2-{3-(piperidine-l-carbonyl)-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2-[2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-ethyl]-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-fluoro-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{4-[(4'-bromo-biphenyl-2-carbonyl)-amino]}-3-
dimethylcarbamoyl-phenyl} -acetoxymethyl) -2 -phenyl-malonic
acid diethyl ester,
2- (2-{.3-dimethylcarbamoyl-4-[ (4 ' -trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid dimethyl ester,
2-cyclopentyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino ] -phenyl} -
acetoxymethyl)-malonic acid diethyl ester,
2-cyclohexyl-2-(2-{3-dimethylcarbamoyl-4-[(4 ' -
trif luorome thyl -biphenyl - 2 -carbonyl) -amino ] -phenyl} -
-acetoxymethyl)-malonic acid diethyl ester,
2- (2-{4-[(4'-chloro-biphenyl-2-carbonyl)-aminoJ-3-
dime thylcarbamoyl -phenyl} - acetoxymethyl) - 2 -phenyl -malonic
acid diethyl ester,
2- (2-{4-[(4'-acetyl-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl-phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{4-[(4'-cyano-biphenyl-2-carbonyl)-amino]-3-
dimethylcarbamoyl -phenyl} - acetoxymethyl) - 2 -phenyl -malonic
acid diethyl ester,
2- (2-{3-dimethylcarbamoyl-4-[(4-methyl-4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2
-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methyl-4'-trifluoro-
me thyl -biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2
-phenyl-malonic acid diethyl ester,
2-[3-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl -
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxy)-propyl]-
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-methoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(5-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(6-methyl-4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid 2,2,2-trifluoroethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{5-dimethylcarbamoyl-2-fluoro-4-[(4f-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-bromo-5-dimethylcarbamoyl-4-[(2'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(3'-fluoro-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(3'-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-(5-
nitro-pyridin-2-yl)-malonic acid diethyl ester,
2-(5-amino-pyridin-2-yl)-2-(2-{3-dimethylcarbamoyl-
4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl}-acetoxymethyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-
pyridin-2-yl-malonic acid diethyl ester,
2-(2-{3-chloro-5-dimethylcarbamoyl-2-fluoro-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2 -(2-{3-bromo-5-dimethylcarbamoyl-2-fluoro- 4-[(4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl} -
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl- 4 -[(4'-trifluoromethyl -
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-o-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluorome thyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) — 2 -m-
tolyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(4'-trifluorome thyl -
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2 -p-
tolyl-malonic acid diethyl ester,
2-(2-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—malonic acid diethyl ester,
2-(3-chloro-phenyl)-2-(2-{3-dimethylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—malonic acid diethyl ester,
2-(4-chloro-phenyl)-2-(2-{3-dime thylcarbamoyl-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-
phenyl-succinic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluorome thyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2- (2-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(3-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(4-
methoxy-phenyl)-malonic acid diethyl ester,
2-(2-{4-[(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{4-[(6-chloro-4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4 -[(6 -fluoro-4'-
trifluoromethyl-biphenyl-2 -carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2- [2-(2-{3-dimethylcarbamoyl-4-|; (5-methyl-4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxy)-ethyl]—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-ethoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(5-isopropoxy-4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)—2-phenyl-malonic acid diethyl ester,
2-[2-(2-{4-(5,4'-bis-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-3-dimethylcarbamoyl-phenyl}-acetoxy)-
ethyl)—2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-(6-methoxy-4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-(3-methyl-4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—
2-phenyl-malonic acid diethyl ester,
2-{2-{4-(2,4-bis-trifluoromethyl-benzoylamino)-3-
dimethylcarbamoyl-phenyl]-acetoxymethyl}—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-methyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-{2-[3-dimethylcarbamoyl-4-(2-ethyl-4-trifluoro-
methyl-benzoylamino)-phenyl]-acetoxymethyl}—2-phenyl-
malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-ethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropenyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl)— 2-
phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-isopropyl- biphenyl-
2-carbonyl) -amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2 -
thiophen-2-yl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-
thiophen-3-yl-malonic acid diethyl ester,
2-(2-{4-dimethylcarbamoyl-5-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-pyridin-2-yl}-acetoxymethyl)—
2-phenyl-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-f(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl)—2- (3-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-(5-
methyl-thiophen-2-yl)-malonic acid diethyl ester,
2-(2-{3-dimethylcarbamoyl- 4 - [ ( 4 ' -trifluorome thyl-
biphenyl - 2 -carbonyl) - amino ] -phenyl} - acetoxymethyl) — 2 -
thiazol-2-yl-malonic acid diethyl ester,
2-(2-{3-ethoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl)— 2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxy-4-[(4'-trifluoromethyl-biphenyl-
2 - carbonyl) -amino ] -phenyl} - acetoxymethyl)—2 -phenyl -malonic
acid diethyl ester.
2-(2-{3-benzyloxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-(2-{3-hydroxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)—2-phenyl-malonic
acid diethyl ester,
2-phenyl-2-(2-{3-piperidin-l-yl-4-[(4'-trifluoro-
me thyl -biphenyl-2 -carbonyl)-amino]-phenyl}-acetoxymethyl) —
malonic acid diethyl ester,
2-phenyl-2-(2-{3-pyrrolidin-l-yl-4-[(4'-trifluoro-
me thyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—
malonic acid diethyl ester,
2-(2-{3-dimethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) —2 -
phenyl-malonic acid diethyl ester,
2-(2-{3-morpholin-4-yl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)—2-
phenyl-malonic acid diethyl ester,
2-(2-{3-diethylamino-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)— 2-
phenyl-malonic acid diethyl ester,
2-(2-{2-chloro-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl)-amino]-benzoyloxy}-ethyl)-2-phenyl-malonic acid
diethyl ester,
2-(2-{3-ethoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(3-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-propionyloxymethyl) -
-2-phenyl-malonic acid diethyl ester,
2-(2-{3-benzyloxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-carboxy-4-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-isopropoxycarbonyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2 -(2-{3-methoxycarbonyl-4-[(4'-trifluoromethyl -
b±phenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-
phenyl-malonic acid diethyl ester,
2-(2-{3-acetylamino-4-[ (4 '-trifluoromethyl-biphenyl-
2-carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic
acid diethyl ester,
2-(2-{3-methoxycarbonylamino-4-[{4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2-(2-{3-(4-methyl-thiazol-2-yl)-4-[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
-2-phenyl-malonic acid diethyl ester,
2-phenyl -2-(2-{6-f(4'-trifluoromethyl-biphenyl- 2 -
carbonyl) -amino] - biphenyl - 3 -yl}- ace toxymethyl) -malonic acid
diethyl ester,
2-(2-{3-formyl-[(4'-trifluoromethyl-biphenyl-2-
carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic
acid diethyl ester,
2-(2-{3-dimethylaminomethyl-4- [ ( 4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) -2-
phenyl-malonic acid diethyl ester,
2 -(2-{3 -(methoxy-methylcarbamoyl)-4 -[(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl)-
2-phenyl-malonic acid diethyl ester,
2- ( 2-{3-isobutyryl-4- [ ( 4 ' -trifluoromethyl-biphenyl-2-
carbonyl)-amino]-phenyl}-acetoxymethyl)-2- phenyl-malonic
acid diethyl ester, and
2-(2-{3-(l-hydroxy-2-methyl-propyl)-4-[(4'-
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl}-
acetoxymethyl)-2-phenyl-malonic acid diethyl ester.
29. The ester compound , or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
4 ' - trifluoromethyl-biphenyl-2-carboxylic acid 4-[2-
phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)-
ethoxycarbonylmethyl]-phenyl ester,
biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-bis-
(2,2 , 2-trif luoro-ethylcarbamoyl) -ethoxycarbonylmethyl]-
phenyl ester,
4 ' -trif luoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis-ethylcarbamoyl-2-phenyl-ethoxycarbonylmethyl) -phenyl
ester,
4 '-trifluoromethyl-biphenyl-2-carboxylic acid 4-(2,2-
bis -ethylcarbamoyl - 2 - phenyl - ethoxycarbonylmethyl) - 2 -
chloro-phenyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis -ethylcarbamoyl-3 -phenyl-propoxycarbonylmethyl) -2-
chloro-phenyl ester,
4 ' -trifluoromethyl-biphenyl-2-carboxylic acid 4-(3,3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl) -phenyl ester,
and
4 '-trifluoromethyl-biphenyl-2-carboxylic acid 4-(3, 3-
bis-ethylcarbamoyl-3-phenyl-propoxycarbonyl} -2 , 6-dichloro-
phenyl ester.
30. The ester compound , Or a pharmaceutically acceptable
salt according to claim
1, which is selected from the group consisting of
2-phenyl-2-{2- [ 4- (4 ' -trif luoromethyl-biphenyl-2-
carbonyloxy) -phenyl] -acetoxymethyl}-malonic acid diethyl
ester,
2-{2- [3-dimethylcarbamoyl-4- ( 4 ' - trif luorome thyl-
biphenyl - 2 - carbonyloxy) -phenyl ] - ace toxyme thyl} - 2 -phenyl -
malonic acid diethyl ester,
2-{2-[3-methoxy-4-(4'-trifluoromethyl-biphenyl-2-
carbonyloxy) -phenyl] -ace toxyme thyl}- 2 -phenyl malonic acid
diethyl ester, and
4- [ ( 4 ' - trif luoromethyl-biphenyl-2-carbonyl) -amino] -
benzoic acid 3-[2-(2,2,2-trifluoro-ethylcarbamoyl)-
naphthalen-1-yl]-propyl ester.
31. The ester compound . or a
pharmaceutically acceptable salt according to claim
1, which is selected from the group consisting of
2-(2-{3-dimethylcarbamoyl-4-[(4'-trifluorome thyl -
biphenyl-2-carbony1)-amino]-phenyl}-acetoxymethyl) -2 -
isopropyl-malonic acid diethyl ester,
2-sec-butyl-2-(2-{3-dimethylcarbamoyl-4-[ (4 ' -
trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl} -
acetoxymethyl)-2-malonic acid diethyl ester,
2- ( 2-{3-dimethylcarbamoyl-4-[(4' -trifluoromethyl-
biphenyl-2-carbonyl)-amino]-phenyl}-acetoxymethyl) -2-
isobutyl-malonic acid diethyl ester,
2- ( 2-{3-dimethylcarbamoyl-4- [ ( 4 ' - trif luoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-ace toxyme thyl) -2-
propyl-malonic acid diethyl ester,
2 - ( 2 - { 3 -dimethylcarbamoyl- 4 - [ ( 4 ' - trif luorornethyl -
biphenyl-2-carbonyl) -amino] -phenyl}-ace toxyme thyl) -2-ethyl
malonic acid diethyl ester,
2-butyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trif luorome thyl-biphenyl-2-carbonyl) -amino ] -phenyl} -
acetoxymethyl) - malonic acid diethyl ester,
2-allyl-2-(2-{3-dimethylcarbamoyl-4-[(4'-
trif luoromethyl-biphenyl-2-carbonyl) -amino] -phenyl}-
acetoxymethyl)-malonic acid diethyl ester,
2- ( 2- {3-dimethylcarbamoyl-4- [ ( 4 ' - trif luoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl}-acetoxy) -2 , 2-bis-
ethoxycarbonyl-propionic acid ethyl ester, and
2- (2-{3-dimethylcarbamoyl-4-[(4'-trifluoromethyl-
biphenyl-2-carbonyl) -amino] -phenyl} -acetoxymethyl) -2-(1-
methyl-butyl)-malonic acid diethyl ester.
32 . 4- [ ( 4 ' -Trifluoromethylbiphenyl-2-carbonyl) a.Tiino] phenyl-
acetic acid 2,2-bisethylcarbamoyl-2-phenylethyl ester.
33 . 4 - [ ( 4 ' -Trif luoromethylbiphenyl -2 -carbonyl j amino ] phenyl -
acetic acid 2,2-bispropylcarbamoyl-2-phenylethyl ester.
34. 2-(2-{3-Ddethylcarbainoyl-4-[(4'- trifIaroniethylbiphenyl-2-carboayl) am sio]
phenyl}acetoxymethy!)-2-phenyhnalonic acid diethyl ester.
35. {3-(pyrrolidine-l-carbonyl)-4-[(4'- trifluoromethyl-biphenyl-2-carbonyl)amino]-
phenyl}-acetic acid 2, 2-bis-ethylcarbamoyl-2-phenyl-etbyl ester.
36. 2-(2-{3-Methoxy-4-[(4'-trifluromethylbiphenyl-2-carbonyl) amino] phenyl}
acetoxymemyl)-2-phenylmalonic acid diethyl ester.
37. An agent, which comprises the ester compound, or a pharmaceutically
acceptable salt according to any of the claims 1 to 36 and a pharmaceutically
acceptable carrier.
38. An MTP (microsomal triglyceride transfer protein) inhibitor, which comprises
the ester compound, or a pharmaceutically acceptable salt according to any of
claims 1 to 36 as an active ingredient.
39. An agent for the treatment or prophylaxis of hyperlipidemia, which comprises
the ester compound, or a pharmaceutically acceptable salt according to any of
claims 1 to 36 as an active ingredient.
40. An agent for the treatment or prophylaxis of arteriosclerosis, which comprises
the ester compound, or a pharmaceutically acceptable salt according to any of
claims I to 36 as an active ingredient.
41. An agent for the treatment or prophylaxis of coronary artery diseases, which
comprises the ester compound, or a pharmaceutically acceptable salt
according to any of claims 1 to 56 as as active ingredient
42. Aa agent for the treatment or prophylaxis of obesity, which comprises the ester
compound, or a pharoiaceutically aeeeptabiesslt according to any of claims 1 to
36 as an active ingredient
36 as an active ingredient
43. An ageat for fbe treatment or prophylaxis of diabetes, which comprises the ester
compound, or a pharmaceutically acceptable salt according to any of claims 1 to
36 as an active ingredient.
44. An agent for the treatment or prophylaxis of hypertension, which comprises tee
ester compound, or a pharm aceutically acceptable salt accordsig to any of claims
I to 36 as an active ingredient.
45. The agent for the treatment or prophylaxis according to claim 37, wherein the
agent is an agent for the treatment or prophylaxis of hyperhpidemia which is
used in combination with other antibyperlipidemic drug(s),
46. The ageent for me treatment of prophylaxis according to claim 45, wherein other
entthyperiipidenmc drug is astatm-type drug.
47. The agent for the treatment or prophylaxis according to claim 46, wherein the
statim-type drug is one or more drug(s) selected from the group consisting of
lovastaiin, simvastatin, pravastatin, fluvastatin, atorvastatm and cerivastarin.
48 . The agent for the treatment or prophylaxis according to claim 37 wherein the
agent is an agent for the treatment or prophylaxis of obzsity which is used in
combination With Other anti-ObeSity drug(s).
49. The agent for the treatment or prophylaxis according to claim 48, where in other
anti-obesity drug is masisdol or/and obesity at.
50. The agent for the treatment or prophylaxis according to claim 37, wherein the
agent is an agent for the treatment or prophylaxis of diabetes which is used in
combination with other anti-diabetic drug(s).
51. The agent for the treatment or prophylaxis according to claim 50, wherein other
anti-diabetic drag is one or more drug (8) selected from the group consistaig of
in sulin preparations, sulfonylursa drugs, insulin secretagogues, ralfonamide
drugs, biguanide drugs, a-glucosidase inhibitors and insulim resistance-
improving drugs.
52 The agent for the treatment or prophylaxis according to claim 50, wherein other
anti-diabetic drug is one or more drug(s) selected from the group consisting of
insulin, glibendamide, to boutamide, glyclopyramide. acetohexamide,
glmepiride, tolaramide, gliclazide, anteglinide, glybuzole, metfomin
hydrochloride, buformin hydrochlonde, boglibose, acarbose and piogltazone
hydrochloride.
53. The agent for the treatment or prophylaxis according to claim 37, wherein the
agent is an agent for the treatment or prophylaxis od hypertension which is used
in combination with other anti-hypertension drug(s).
54. The agent for (he treatment or prophylaxis according to claim 53, wherein other
anti-hypertension drug is one of more drug (s) selected from the group consisting
of loop diuretics, angiotensin converting enzyme inhibitors, angioteasin II
receptor antagonists, calcium antagonists, b-blockers, a, b-b!ockers and a-
b lockers.
55. The agent for the treatment or prophylaxis according to claim 53, wherein other
anti-hypertension drug is one or more drug(s) selected from the group consisting
of furoseaitcb delayed release, captopril captopril delayed release, enalapril
maleate,, alaeepril,. delapnl hydrochaioride, silazapril, lismopnil, benazepril
hydriothloride, hydrocaloride, temocapril hydrochloride, qamapril
hydroshloride, trandciapril, perindopril erburafee, losartaan ,
cacdesartan cilexetil, nicardiptne hydrochloride, nicardipine hydrochloride
delayed release, nilvadipine, nifedipine, aifedipine delayed release, beoidipine
hydrochloride-, diltiazen hydrochloride, diliiazem hydfoehloride delsyed release,
nisoidipine, nitrendipine, manidipsine hydrochlofide, baraidipine hydrochloride,
efonidpine hydrochloride. besylate felodgipine cilnidipine,
sranidipine, prepranolol baydrochlorids, prepranofctl hydrochforide delayed
release, pindolol, pindolol delayed release in denolol hydraehloride, carteolol
hydrocbloride, carteolol hydrodhloride defayed release, bunitrolol hydfochloride,
bunitrolol hydrochlonde delayed release, atenolol agebutolol hydro chloride,
metoprolol tartrate, metoprolol tarfrateate delayed release, nipradilol penbutolol
sulfate, tilusolol hydrochloride, carvedlioi, bisoprolot fumarate, betaxolol
hydrochloride, celiprolol hydrochloride, bopmdolol malonate, bevantolol
hydro chloride, labetalol hydrochloride, arotinolol hydrochloride, amosulabt
hydrochloride, prazosin hydrochloride, terazosin hydrochionde, doxazosin
mesty, bonazocin hydrochionde, tunazocin bydrochlaride delayed release,
urapidi! and pheetoiamme mesylste.

56. A pharmaceutical composition comprising an effective amount of the
ester compound, or a pharmaceutically acceptable salt according to any
of claims 1 to 36, a pharmaceutically acceptable, appropriate amount of
ethanol and propylene glycol fatty acid.
57.The pharmaceutically composition according to claim 56, which
comprises 25 to 35% by weight of ethanol and 65 to 75% by weight of
propylene glycol fatty acid ester.
58. A capsule of formulation comprising the pharmaceutical composition
according to claim 56 or claim 57.
59.The capsule formulation according to claim 58, wherein the capsule
formulation is a hard capsule or soft capsule.
60. An ester compound according to claim 1 which is 4-{(4'-trifluoro-
methyl-biphenyl-2-carbonyl)-amino ] - phenyl -acetic acid 2,2-bis-
ethylcarbamoyl -2-phenyl-ethyl ester, or a pharmaceutically acceptable
salt thereof.
61.An ester compound according to claim 1 which is 4- [ (4'-trifluoro-
methyl biphenyl-2-carbonyl)-arnino]-phenyl -acetic acid 2-phenyl-2-,2-
bis-propylcarbamoyl-ethylester, or a pharmaceutically acceptable salt
thereof.

62. An ester compound according to claim 1, which is 2-(2- 3-
dimethylcarbamoyl-4-[ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-
phenyl acetoxymethyl)-2-phtnyl-milonlc acid diethyl ester, or a
pharmaceutically acceptance salt thereof.
63. An ester compound as claimed in claim 1, which is 3-diethylcarbamoyl-
(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-phenyl -acetic acid 2,2-
bis - ethylcarbamoyl-2-phenyl-ethyl ester, or a pharmaceutically
acceptable salt thereof.
64. An ester compound accordin to claim 1, which is 2-(2- 3-
dicthylcarbamoyl-4- [ (4'-trifluoromethyl-biphenyl-2-carbonyl)-amino ]
-phenyl -acetoxymethyl)-2-phenyl-malonic acid diethyl ester, or a
pharmaceutically acceptable salt thereof.
65. An ester compound as claimed in claim 1 which is 3-methoxy-4- [(4'-
trifluoromcthyl-blphenyl-2-carbonyl)-amino] -phenyl -acetic acid 2,2-bis-
ethylcarbamoyl-2-phenyl-ethyl ester, or a pharmaceutically acceptable salt
thereof.
66. An ester compound as claimed in claim 1, which is 2-(2- 3-methoxy-4-
[(4'-trifluoromethyl-biphenyl-2-carbonyl) - amino ] - phenyl
acetoxymethyl) -2-phenyI - malonic acid diethyI ester, or a
pharmaceutically acceptable salt thereof.

A novel therapeutic agent for hyperlipidemia, which is as ester compound
represented by the formula (1")
(wherein R1 and R2 are each hydrogen atom or optionally substituted aryl, etc.; X is -
COO- or -CON (R10)-; R3 and R4 are each hydrogen atom, C1-C6 alkyl or C1-C6
alkoxy, etc.; R5 and R6 are each hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy, etc; R8
and R9 are each independently hydrogen atom, C1-C6 alkyl -CON (R18) (R19) Of -
COO (R20 ), etc.; ring A, ring B and ring C are each independently aryl or heterocycle
residue, etc.; Alk1 and Alk2 are each independently alkanediyl, etc.; 1 and m are each
an integer of 0 or 1 to 3) or a prodrug thereof, or a pharmaceutically acceptable salt of
either. The therapeutic agent selectively inhibits MTP in the small intestine, thus
causes no such side effect as a fatty liver.

Documents:

460-KOLNP-2004-(07-12-2011)-FORM-27.pdf

460-KOLNP-2004-FORM 27.pdf

460-kolnp-2004-granted-abstract.pdf

460-kolnp-2004-granted-claims.pdf

460-kolnp-2004-granted-correspondence.pdf

460-kolnp-2004-granted-description (complete).pdf

460-kolnp-2004-granted-examination report.pdf

460-kolnp-2004-granted-form 1.pdf

460-kolnp-2004-granted-form 13.pdf

460-kolnp-2004-granted-form 18.pdf

460-kolnp-2004-granted-form 2.pdf

460-kolnp-2004-granted-form 26.pdf

460-kolnp-2004-granted-form 3.pdf

460-kolnp-2004-granted-form 5.pdf

460-kolnp-2004-granted-reply to examination report.pdf

460-kolnp-2004-granted-specification.pdf


Patent Number 233999
Indian Patent Application Number 460/KOLNP/2004
PG Journal Number 18/2009
Publication Date 01-May-2009
Grant Date 29-Apr-2009
Date of Filing 07-Apr-2004
Name of Patentee JAPAN TOBACCO INC.
Applicant Address 2-1, TORANOMON 2-CHOME MINATO-KU, TOKYO 105-8422
Inventors:
# Inventor's Name Inventor's Address
1 HAGIWARA ATSUSHI C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
2 OE YASUHIRO C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
3 KAWAI TAKASHI C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
4 TANIGUCHI TOSHIO C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
5 ODANI NAOYA C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
6 WATANABE SHIZUE C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
7 IKENOGAMI TAKU C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
8 MADONO KENYA C/O CENTRAL PHARMACEUTICAL RESEARCH INSTITUTE OF JAPAN TOBACCO INC., 1-1, MURASAKICHO, TAKATSUKI-SHI, OSAKA 569-1125
PCT International Classification Number C07C 69/732
PCT International Application Number PCT/JP2003/02398
PCT International Filing date 2003-02-28
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 2002-53876 2002-02-28 Japan