AU2005248950A1

AU2005248950A1 - Ester compound and medicinal use thereof

Info

Publication number: AU2005248950A1
Application number: AU2005248950A
Authority: AU
Inventors: Atsushi Hagiwara; Taku Ikenogami; Takashi Kawai; Kenya Madono; Naoya Odani; Yasuhiro Ohe; Toshio Taniguchi; Shizue Watanabe
Original assignee: Japan Tobacco Inc
Current assignee: Japan Tobacco Inc
Priority date: 2002-02-28
Filing date: 2005-12-23
Publication date: 2006-01-19

Description

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Applicant: JAPAN TOBACCO INC.

Invention Title: ESTER COMPOUND AND MEDICINAL USE THEREOF The following statement is a full description of this invention, including the best method of performing it known to me/us: C(

.DESCRIPTION

ESTER COMPOUND AND MEDICAL USE THEREOF ci Technical Field Oh The present invention relates to a novel ester compound, 00 and also relates to a pharmaceutical composition comprising a Ifl novel pster compound which selectively inhibits microsomal O 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 CN 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 c administration, and acquired hyperlipidemia basically resulting from overnutrition.

I Meanwhile, lipid taken in from food is absorbed in the 00 small intestine by the action of bile acid, and secreted as in chylomicron in the blood via lymphatic vessels. The 0 O 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 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 cN separated from microsomal fractions of bovine liver by Wetterau C) 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 Sthe deficit of MTP. In other word, the disease is characterized 00 4 in that, while the genes related to apolipoprotein B are normal, ci I) apolipoprotein B is hardly detected in the serum, the level of O 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 C VLDL in the liver or as chylomicron in the small intestine. It Sshould be said that MTP is indispensable for the construction en of those lipoproteins. Namely, if the activity of MTP is blocked, the transfer of lipid such as TG and CE, etc. to O 5 apolipoprotein is inhibited, whereby formation of a lipoprotein 0\ can be inhibited.

00 SOn the other hand, it has been elucidated that LDL in ci n general is closely related to the progression of 0 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 c N prophylaxis of pancreatitis, hypercholesterolemia,

O

hyperglyceridemia, etc. has been expected to be provided.

SHowever, with the development of MTP inhibitors, some cases of fatty liver were reported and concern over O 5 hepatotoxicity has been raised.

Sh For these reasons, a novel MTP inhibitor causing no side 00 4 effect such as a fatty liver, etc. has been strongly desired.

VI In the conventional manners, combined therapies of 0 various combinations of different antihyperlipidemic drugs have been tried. However, when, for example, a statin-type drug and a resin-type drug 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 W097/26240.

c) o

CF

3

SCF

3 S HNN

H

00 O The following compound is disclosed in W097/43257.

0 0 A- N NNH C The following compound is disclosed in W098/23593.

CF

3 N N The following compound is disclosed in W99/63929.

N

The following compound is disclosed in W099/63929.

The following compound is disclosed in W02000/5201.

The following compound is disclosed in J. Med.

Chem.(2001), 44(6) p.851-856.

CF,1 The following compound is disclosed in EP 1099701.

CF3 N/

R

1 0 N n R2 N N

R

The following compound is disclosed in W02001/77077.

The following compound is Chem.(2001), 44(6) p.4677- 46 87.

CF

3 MeI

NHCO

2 Mf Me, Ji 2

L

disclosed in J. Med.

The following compound is disclosed in W02002/4403.

RI

R1 [R7 S0 00 R3 o 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

O

(N selectively inhibits MTP in the small intestine but Usubstantially 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 is immediately Smetabolized in the small intestine, blood or liver, which makes V) it possible for the compound to selectively affect MTP in the Ssmall 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 esterified 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, Cq thus potently inhibit MTP in the small intestine and significantly lower triglyceride and cholesterol in blood. In n addition, the compounds of the present invention significantly lower non-HDL cholesterol and, surprisingly, increase plasma S 5 HDL cholesterol.

Accordingly, the inventors of the present invention have 00 Sfound that when a compound comprises the ester structure ci S represented by the below-mentioned formula the compound Sis 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 An ester compound represented by the formula (1) R2

R

4 0 D A X B (Alk) 0-(Alk2) R8 (1) R9 R3 wherein

R

1 and R 2 are each hydrogen, Ci-C 6 alkyl, C3-C 7 cycloalkyl, Cz-C 6 alkoxy; halo C 1

-C

6 alkyl, halo C 1

-C

6 alkyloxy, optionally substituted C 6 -Cz4 aryl, optionally substituted C7-C 6 aralkyl, optionally substituted C 6 -Cz 4 aryloxy, optionally substituted C7-C 16 aralkyloxy, optionally substituted C7-C 1 5 arylcarbonyl, optionally substituted heterocycle, C2-C 7 alkoxycarbonyl, halogen, C 2

-C

6 alkenyl, -N(R 40

(R

41 wherein R 40 and R 41 are each independently hydrogen or optionally substituted C 6

-C

14 aryl; ring A is C 6

-C

14 aryl, heterocycle, or ci oor X is -COO-(CH 2

-CON(R'

i

(C

H 2 or -N(R 1 o CO CH2 6 Sowherein R i0 is hydrogen, C 1 -C alkyl or C 3

-C

7 cycloalkyl and n O is an integer of 0 to 3; substituted heterocycle, -CON(R" (R 2 (wherein R 1 and R 12 are each independently hydrogen, C 1

-C

6 alkyl, optionally substituted C6-C14 aryl, optionally substituted C7-C 16 aralkyl,

C,-C

6 alkoxy, or R 11 and R 1 2 may be taken together with the nitrogen to which they are attached to form -N -N 0 or Swherein p is an integer of 0 to -(CH 2 )q-N(R 13

)(R

14 (wherein

R

13 and R 14 are each independently hydrogen, CI-C 6 alkyl, C 2

-C

7 alkoxycarbonyl, Ci-C 6 acyl, or R 13 and R 1 may be taken together with the nitrogen to which they are attached to form -N )p -N 0 or wherein p has the same meaning as defined above and q is an integer of 0 to or -CO(R1 5 )(wherein R 15 is hydroxy, Ci-C 6 alkoxy, optionally substituted C 6

-C

14 aryloxy, optionally substituted C 7

-C

16 aralkyloxy or C 1 -C alkyl); ring B is

A

K KNK

N-

N

A 'N N K

A

K

A N 04 4):N-

N

A x:N*

S

H

N

wherein K is an integer of 0 to 2, or ring B may be taken together with R 3

R

10 and the nitrogen bound to R' 0 to form

-N.

Alki' is alkanediyl or alkenediyl; Alkl 2 is alkanediyl or alkenediyl; 0 c( 1 is an integer of 0 to 3; 1 m is an integer of 0 to 3; en D is Ci-C 6 alkyl. C 2

-C

6 alkenyl, C 2

-C

7 alkoxycarbonyl,

-N(R

4 2

)-CO(R

43 (wherein R 4 2 is hydrogen or C 1

-C

6 alkyl and R 43 is O 5 C 6

-C

14 aryl or C 7

-C

1 6 aralkyl), or the group represented by the O\ following formula I RS

R

7 00 o C (wherein R 5

R

6 and R 7 are each independently hydrogen, CI-Cs alkyl, CI-C alkoxy, C 2 -C7 alkoxycarbonyl, carboxyl, halogen, cyano, nitro, halo CI-C 6 alkyl, Ci-C 6 acyl, hydroxy, amino, optionally substituted' C6-C14 aryl, or

-(CH

2 )r-CON(R 6

(R

17 (wherein R 16 andR 17 are each independently hydrogen, Ci-C 6 alkyl or halo Ci-C 6 alkyl and r is an integer of 0 to 3); ring C is C 6

-C

1 4 aryl, C 7

-C

15 arylcarbonylamino, C 8

-C

17 aralkylcarbonylamino, heterocycle residue, C 3

-C

7 cycloalkyl or

C

7 -Ci 6 aralkyl, or ring C may be taken together with R 7 and R 8 to form and

R

8 and R 9 are each independently hydrogen, CI-C 6 alkyl, optionally substituted C 6

-C

14 aryl, hydroxy C 1

-C

6 alkyl, c -CON(R1) (R" (wherein R 18 and R 19 are each independently hydrogen, C 1

-C

6 alkyl, C3-C7 cycloalkyl, halo CI-C 6 alkyl, C 2

-C

1 2 alkoxyalkyl or optionally substituted C 6

-C

1 4 aryl), -COO(R 20 or

C

N

-(CH

2

),-OCO(R

0 (wherein R 20 is hydrogen, Ci-C 6 alkyl or C 3

-C

7 cycloalkyl; s is an integer of 0 to -N(R 21 2 2

(R

22 (wherein R 21 n and R 22 are each independently hydrogen, CI-Cs alkyl, CI-Cs acyl,

C

1

-C

6 alkylsulfonyl, or R 2 and R 2 may be taken together with V) the nitrogen to which they are attached to form

-N

0 or

R

B and R 9 may be taken together to form C 3

-C

7 cycloalkyl, or a prodrug thereof, or a pharmaceutically acceptable salt of either; The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above wherein D is Ci-C6 alkyl, C 2

-C

6 alkenyl, C 2

-C

7 alkoxycarbonyl or -N(R 42

)-CO(R

43 in which R 42 and R 43 each has the same meaning as defined above; The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above wherein D is the group represented by the formula 6 o I R7

CC)

in which R 5

R

6 and R 7 each has the same meaning as defined above: 00 Ci V) The ester compound or a prodrug thereof, or a o 5 pharmaceutically acceptable salt of either according to the above wherein the ring C is

S

Sor ,in which q is an integer of 0 to 3; The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above or wherein ring B is or The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above wherein ring A is 00 Cor ci o The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the 00 5 above wherein X is -CON(R 1 0 in which R0 and n each ci ohas the same meaning as defined above; ci The ester compound or a prodrug thereof, or a pharmaceutically acceptablesalt of either according to the above wherein X is -CO0-(CH 2 in which n has the same meaning as defined above; The ester compound- or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above wherein n is 0; The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is represented by the formula

R

6 21 2

C

j R7 4 0 0 h CH (1 R x] R9 I

I

wherein c R 2 'and R 2 are each independently hydrogen, Ci-C 6 alkyl,

O

J C 3

-C

7 cycloalkyl,

CI-C

6 alkoxy, halogen, halo Ci-C 6 alkyl, Ci-C 6 n acyl, C 2

-C

6 alkenyl or cyano; XI is or -NR 10 wherein R" 1 is hydrogen. C 1 -Cs alkyl 5 or C 3 cycloalkyl; and R R, R R 5 R. R 7

R

8

R

9 ring C, 1 and m each has 00 the same meaning as defined above, n or a prodrug thereof, or a pharmaceutically acceptable salt of Seither; (11) The ester compound or a prodrug thereof, or a pharnaceutically acceptable salt of either according to the above wherein the ring C is s or 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 wherein X 1 is -NR 10 in which R 1 0 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 wherein XI is 0) n (14) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the O 5 above (10) to wherein the group -(CH2)1- is located at C0 the h-position of the benzene ring in the formula 00 o (15) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above (10) to wherein the group -(CH 2 1 is located at the i-position of the benzene ring in the formula (16) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above (10) to wherein R a and R 9 are each independently

-CON(R'

8 in which R 18 and R 19 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 wherein R 8 and R 9 are each independently

-COO(R

20 in which R 20 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 wherein the ring C is C 6

-C

14 aryl; (19) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the CA above wherein C 6

-C

14 aryl is phenyl; The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above (12) to wherein the ring C is C 3 -C7 cycloalkyl; 00 (21) The ester compound or a prodrug thereof, or a VS pharmaceutically acceptable salt of either according to the C above (12) to wherein the ring C is or

S

(22) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of (4-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-aminolphenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phenyl-ethyl ester, 2-phenyl-2-{2-[4-(4'-trifluoromethyl-biphenyl-2carbonyloxy)-phenyl]-acetoxymethyl)-malonic acid diethyl ester, 2-(2-{3-methyl-4-[(4'-trifluoromethyl-biphenyl-2carbonyl)-amino]-phenyll-acetoxymethyl)-2-phenyl-malonic acid diethyl ester, 2-(2-{4-[methyl-(4'-trifluoromethyl-biphenyl-2carbonyl)-amino]-phenyl}-acetoxymethyl)-2-phenyl-malonic acid diethyl ester, {3-ethyl-4-[(4'-trifluoromethyl-biphenyl-2-cabonyl)- (Namino] -phenyl)l-acetic acid 2, 2-bis-ethylcarbamOyl-2phenyl-ethyl ester, M{ 4- -trifluoromethy1-biphenyl-2-carbonYl) -amino] phenyl)-acetic acid 9-(2 2-trifluoro-ethylcarbanoyl) -9hfluoren-9-ylmethyl ester, 2-(4-17(4'-trifluoromethyi-biphenyl-2-CarbOl-) 00 '4 amino] -phenyl}-propionic acid 9- 2-trifluoro- S) ethylcarbamoyl) -9h-fluoren.-9-ylmethyl ester, (N -trifluoromethyl-biphelyl-2-Carbolyl) -amino] phenyl)-acetic acid 2-phenyl-2-(2,2,2-triflloroethylcarbamoyl) -ethyl ester, 2-phenyl-2-(2-{4-[(4'-trifluoromethyl-biphelyl-2carbonyl) amino -phenyl}-acetox-ymethyl) -malonic acid diethyl ester, -trifluoromethyl-biphenyl-2-carbOnYl) -amino] phenyl)-acetic acid 2,2. 2-trifluoro-ethylcarbanoy.) cyclopentylmethyl ester, 2-phenyl-2-(2-t4-[ (4'-triiluoromethyl-biphenyl-2carbonyl) -amino] -phenyl)-acetoxyethyl) -malonic acid diisopropyl ester, (4-17(4' trif luoromethyl -biphenyl- 2- carbolyl) amiLno] phenylil-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluoroethylcarbamoyl) -ethyl ester, 2-phenyl-2- (2-114-1(4' -trifluoromethyl-biphenyl-2carbonyl) -amino] -phenyl)-acetoxymethyl) -malonic acid diinethy. ester.

2-cyclopentyl-2- '-trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyll-acetoxymethyl) -malonic acid diethyl ester, [(4'-trifluoromethyl-bipheny1-2-carbonyl) -amiLno] phenyl}-acetic acid 1- 2,2-trifluoro-ethylcarbI l) cyclohexylmethyl ester.

2-phenyl-2-(2- (2-trifluoronethyl-belZOylamilO)o 5 phenyl]-acetoxymethyl-falOliC acid diethyl ester, 2-{2-.[4-(2-phenoxy-belzoylaliflO)-pheflYl]- 00 '4 acetox-ymethyl-2-phelyl-lalOliC acid diethyl ester, 0' 2-.2-[4-(2-butoxy-benzoylamilo}-phel]o acetoxymethyl}-2-phelYl-malOlic acid diethyl ester, 2-phenyl-2-!12- (2-trifluoromethyl-befzllOXY) phenyl]-acetorymethyl-malOlic acid diethyl ester, 2-{2-'[4-(2-benzoyl-beflzoyloxy)-PhelYllacetoxymethyl)-2-PhelYl-faloflic acid diethyl ester, (2-benzoyl-benzoylamilo) -phenyl] acetoxymethyl-2-phelyl-alOflic acid diethyl ester, 2-phenyl-2-(2-(4-L (4'-trifluoromethyl-bipheflYl-2carbonyl) -amino] -phenyl}-acetoxylethyl) -malonic acid dicyclohexyl ester, {44 -trifluorornethyl-biphelyl- 2-carbonyl) -am~ino] phe nyl)-acetic acid 2, 2-bis-cyclohexylCarbamfoYl-2-Pheflethyl ester, [(41 -trif luoromethy.-bipheiyl-2-CarbOfl) -amino] phenyl}-acetic acid 2-phenyl-2 ,2-bis-phenylcarbamoyl-ethyl ester, -trifluoromethyl-biphenyl-2-crbOflYl) -amino] phenyl)-acetic acid 2, 2-bis-isopropylcarbanoyl-2-phelylethyl ester, 2-benzyl-2-(2-(4-[(4'-trifluoromlethyl-bipheflyl-2carbonyl) -amino -phenyl)-acetoxcymethyl) -malonic acid diethyl ester, 2-(2-{2-methyl-4-[ (4'-trifluOrOflethyl-biPheflYl-2 en carbonyl) -amino]I -phenyl}-acetOx-ymfethYJ.) -2-phenyl-malonic acid diethyl ester, o 5 4' -trifluoromethyl-biphenflJ2-CarbQ]Wlic acid 4- [2phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)- 00 ethoxycarbonylrnethyl I-phenyl ester, Vo biphenyl-2-CarbOXYliC acid 4- [2-phenyl-22-bis- 2,2- 0 trifluoro-ethylcarbafOYl) -ethoxycarbonylmethyl] -phenyl ester, 2-butoxy-benzoic acid 4-[2-pheny1-2.,2-bis-(2,2,2trifluoro -ethylcarbamoyl) -eth oxycarbonylmethYl] -phenyl ester, 2-cyclohexyl-2-(2-{4-[ (4'-trifluoromethYl-biPheflyl-2carbonyl) -amino] I phenylI}-acetoxymethY.) -malonic acid diethyl ester, (biphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2-phenyl-2, 2-bis- (2,2,2-trifluorO-ethylCab.IfOyl) -ethyl ester, [4-(2-phenoxy-benzoylamilO) -pbhenyl] -acetic acid 2phenyl-2,2-bis- 2-trifluorO-ethylCarbamOyl) -ethyl ester, 2-phenyl-2- (2-{2-trifluoromethyl-4- trifluoromethyl-biphelyl-2-CarbOlYl) -amino] -phenyl)acetoxyrnethyl)-malOflic acid diethyl ester, -trifluoromethyl-biPhelYl-2-carbOlYl) -amino) phenyll-acetic acid 2 -phenyl-2 ,2-bis -propylcarbafOyl -ethyl ester, (4 [(41 -trifluoromethyl-bipher1Y1-2carbOlYl) -ami-no] phenyl)-acetic acid 2,2 -bis -me thylcarbX l 2- phenl'lethyl ester,' 2-pyridiri-2-yl-2-(2-{ 4 -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl}-acetOsylethYl) -ialonic acid diethyl ester, 2-pyridin-3-yl-2-( 2 4 (4'-trifluornnethYl-biPhelYl- 00 2-carbonyl) -amino] -phenyl}-acetoxyfethyl) -malonic acid diethyl ester, 0 4' trifluororethyl-bipheyl-l2-CarbOXYliC acid 4- (2,2bis -ethylcarbanoyl -2 -phenyl-ethoxyCarbOlylIthYl) -phenyl ester, 2-phenyl'-2-(2-t3-trif1uoromfethyl-44[( 41 trifluoromethyl-biphelyl- 2 -carbonyl) -amino] -phenyll acetoxymethyl)-rnalonic acid diethyl ester, (2-butoxy-benzoylamilo) -phenyl] -acetic acid .2-phenyl-2, 2-bis- 2-trifluoro-ethylcarbwnoYl) -ethyl ester, 4- -trifluoromethyl-biphenyl- 2-carbonyl) -amiLno] phenyfl-acetic acid 2, 2-bis-butylcarbamoyl-2-pheflyl-ethyl ester.

2-(2-{4-[(9-oxo-9h-fuorene--carbOly1)-amUro]phenyl}-acetoxymethyl)-2-Phel-alOliC acid diethyl ester, 2-(2-{4-[(9h-fuorene--carbOy)-ainl-phenYJlTh acetoxymethyl) -2-phenyl-malonic acid diethyl ester, {3-methyl-4-[1(4' -trifluoro'nethyl-biphenyl-2carbonyl) -amino] -phenyl) -acetic acid 2, 2-bis-ethylcarbamoyl- 2-phenyl-ethyl ester, 2-(2-{4-[(4'-methy1-bipheflyl-2-carbofl)-amiflo] phenyl}-acetoxylethyl) -2-phenyl-malonic acid diethyl ester, C) pheny1)--acetoxymlethy1-2-PhelJmalOnic acid diethyl ester, -trifluoromethyl-biphenl2-cabonyl) -aino)]phenyl}-acetic acid 3, 3-bis-ethylcaxrbamOy1-3-PheflYl-PrOPYl ester, -trifluoromethy-biphenfly-2-CarbOlYl) -amino] 00 '4 phenyl}-acetic acid 3-phenyl-3. 3-bis-propylcarbwfloyl-PrOPY1 ester, o 4- (biphenyl- 2-carbOlYl) -amino] -phenyl)l-acetic acid 2, 2-bis-.ethylcarbamoy1-2-pher1Y1-BthYl ester, 2-phenoxy-benzoylalifO) -phenyll-acetic acid 2, 2-bis-ethylcarbamoy1-2-pheIny1-ethYl ester, (2-butoxy-benzoylalilO)-Phell-acetic acid 2, 2-bis-ethylcarbamfly-2-phefylyethYl ester, 2-phenyl-2-(2-(4-[(3' -trifluoromethy1-biPhefl-2carbonyl) -amino] -phenyl}-acetoxynethYl) -malonic. acid diethyl ester, 2-2(-2(-loobnoy)bnolmnlpey) acetoxymethyl)-2-phelyl-falOflic acid diethyl ester, 4' -trifluoromethy1-bipherny1-2-carbOXYlic acid 4- (2,2bis -ethylcarbamoyl-2 -phenyl-ethoxcycarbOflYlmethyl) chiorophenyl ester, 2-hnl2(-4(-hope--lbnolmn) phenyl]-acetoxymethyl-falOflic acid diethyl ester, 2- (bipheny-3-carbol) -amlinlo)-phefl) acetoxymethyl) -2-phenyl-inaloflic acid diethyl ester, [isopropyl-(4 '-trifluoromethyl-biPhelYl-2carbonyl) -amino] -phenyl) -acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-f4-[Icyclohezq l- -trifluoromethyl-biphelyl-2carbonyl) -amino]I -phenyl}-acetoyfethyl) -2-phenyl-ialonic en acid diethyl ester, 2-(2-[4-(2-isopropy-belzoyailo)-phelo 5 acetoxyinethyl)-2-phelyl-malOliC acid diethyl ester, 2-{2-II4-(2-benzy-bnzoy8Ifilo)-Phefl]- 00 acetoxymethyll -2 -phenyl-inalonic acid diethyl. ester, 0) 2-phenyl-2-(2-{4-I(4'-trifluoronethyJ--bipheflYl-2c-icarbonyl) -amino] -phenyl}-acetoxymethYl) -malonic, acid dipropyl. ester, 2-phenyl-2-(2-{4-[ -trifluoromethyl-biphenyl-2carbonyl) -amino) -phenyl-acetoxyfethy.) -malonic acid dlisobutyl ester, 2-phenyl-2-(2- (2-trifluoromethoxy-belzoylamlO) phenyl]-acetOxymfethYl)-malOflic acid diethyl ester, 2- (2-butoxycarbonyl-benZOylaminO) -phenyl 1acetoxymethyl) -2 -phenyJ.-maloflic acid diethyl ester, -trifluoromethyl-biphenyl-2-CarbOl)-amino] phenyl)-acetic acid 2, 2 -bis- isobutylcarbamoyl-2 -phenl -ethyl ester, -trifluoromethyl-biphelyl-2-CarbOlyl) -amino) phenyl}-acetic acid 2,*2-bis- (3-methyl-butylcarbamoyl) -2phenyl-ethyl ester, 2-(2-{4-[ethyl-(4' -trifluoroxnethyl-biphenyl-2carbonyl) -amino] -phenyl-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, (2-cyclohexyl-benzoylamino) -phenyl] -acetic acid 2, 2-bis-ethylcarbalOyl-2-phekyl-ethy- ester, (4'-chloro-biphenyl-2-Carboflyl)-amil]-phelyl)acetic acid 2,2-bis ethylcarbamOy1-2-Phel-ethYl ester, ,4'-dicbloro-biphenfly-2-CarbOfl)-amfiflO en phenyl)-acetic acid 2, 2-bis-ethlycarbaxnoy1-2-Phenfl-etbY1 ester, o 5 {3-methyl-4- -trifluoromethy1-biPhenfl-2carbonyl)-amino]-phenyl)-acetic acid 2-phenyl-2,2-bis- 00 propylcarbamoyl-ethyl ester, V' -trifluoronethy1-bipel-2-CrbOlYl)-ami-no]- 0 phenyl)-acetic. acid 2, 2-bis- (2-methoxy-ethylcarbafoyl) -2phenyl-ethyl ester, 2- [2-methyl-4- (4-trifltloromethyl-PhelYl)- -axino)-phenyl) -acetoxymethyl) -2phenyl-malonic acid diethyl ester, [2-methyl-4-(4-trifluOromethYl-PhelYl) -thiazole- 5-carbonyl] -axino}-phenyl)-acetic acid 2 ,2-bisethylcarbaxnoyl-2-phenyl-ethyi ester, (4-trifluoromethyl-phelyl) -pyridine-3carbonyl]I amino) -phenyl) acetic acid 2, 2 -bis -ethylcarbanoyl 2-phenyl-ethyl ester, (3-methyl-4-( [2-(4-trifluoromethyl-PheflYl) -pyridine- 3-carbonyl] -aznino}-phenyl) -acetic acid 2 ,2-bisethylcarbamoyl-2-phenyl-ethyl ester,' 2-(2-(3-ethy1-4-[(4'-trif1uoromethy-biphel-2carbonyl) -amino) -phenylj-acetoxy'ethyl) -2-phenyl-malonic acid diethyl ester, {3-isopropyl-4- -trifluoromethyl-biphelyl-2 carbonyl) amino] -phenyl) -acetic acid 2, 2 -bis -ethylcarbatoyl 2-phenyl-ethyl ester, 2-{3-isopropyl-4- 1(4' -trifluoromethyl-biPhel-2carbonyl) -amino] -phenyl)-acetoxynethyl) -2-phenyl-malonic acid diethyl ester, en {3-ethyl-4- -trifluoromethY1-biPhel-2-carbOlYl) amino] -phenyl}-acetic acid 3, 3-bis-ethylcarbafoyl- 3-phenyl-prOpyl ester, {3-isobutyl-4- -trifluorornethY1-biPhefl-2 00 carbonyl) amino]I -phenyl)l-acet ic acid 2, ,2-bis -ethylcarbamrfl o 2-phenyl-ethyl ester, 0 2-(2-{3-iSObUtyl-4-[ -tritluoromethyl-biphelYl-2carbonyl) amino]I phenyl)}-acetOkymethYl) 2 -phenyl -malonic acid diethyl ester, 2-(2-(3-chlOrO-4-[ (4'-~trifluoromethy1-biphefl-2carbonyl) -amino] -phenyi1-acetOXymfethYl) -2-phenyl-malolic acid diethyl ester, 2-2{-rm--('tifurmty-ihnl2 carbonyl) -amino] -phenyl}-acetoxyfethYl) -2-phenyl-malonic acid diethyl ester, -dirnethylcarbamoyl 4- trif luoromethyl -biphelyl 2-carbonyl) -amino] -pheryl)-acetic acid 2 ,2-bisethylcarbamoyl- 2-phenyl-ethyl ester, -dimethylcarbafoyl -4 trif luoromethyl -biphelyl 2-carbony) -amlifo]-phenylY -acetic acid 2-phenyl-2,2-bispropylcarbamoyl-ethyl ester, f{3-methylcarbaloyl-4- -trif luoronethyl-biphel-2carbonyl) amino -phenyl) -acetic acid 2, 2 -bis -ethylcarbamTOy1 2-phenyJ.-ethyl ester, 3 -diniethylcarbamoyl -4 trit luoromethyl -biphenyl 2-carbonyl) -amino] -phenylj-acetic acid 3, 3-bisethylcarbamfoyl- 3-phenyl-propyl ester, 2- dime thycarbafOyl:-4-[( 4 -trif luoromethylbiphenyl- 2-carbonyl) -amino] -phenyl) -acetos-ymethyl) -2en phenyl-malonic acid diethyl ester, {3-benzy-carbafoyl-4- -trifluoromethy-biPhel-2carbonyl)- amino] -phenyl}I-acetic acid 2, 2-bis-ethYCSrb~mOY- 2-phenyl-ethyl ester, 00 {3-dimethylcarbaxnOyl-4- -trifluoromethyl-biPhenfl o2-carbonyl)-amino]-pheflyl)-acetic acid 4,4- bis- 0 ethylcarbamoyl-4 -phenyl-butyl ester, (3 -diethylcarbamoyl- 4- -trif luoromethY1-biPhel1 2-carbonyl) -amino] -phenyl)-acetic acid 2 ,2-bisethylcarbamoyl-2-pheflyl-ethYl ester, {3-diisopropylcarbaly-4- -trifluoromethylbiphenyl-2-carbolyl) -amino] -phenyl)-acetic acid 2. 2-bisethylcarbamoyl-2 -phenyl-ethyl ester, 2- (2 {3-diethylcarbamoy1 -trifluoromethylbiphenyl-2-carbOlyl) -amino) -phenyl)-acetOxYlfethYl) -2phenyl-malonic acid diethyl ester, 2- (2-{3-diisopropylcarbamOyl-4-[ -trifluoromethylbiphenyl- 2-carbonyl) -ami-no] -phenyl) -acetoxymethyl) -2 -phenylnialonic acid diethyl ester, {3-(isopropyl-methyl-carbafOyl) 4 trifluoromethyl-biphelyl-2-carbOlYl) -amino] -phenyl)-acetic acid 2,2-bisethylcarbanoyl-2 -phenyl-ethyl ester, 2-(2-{3-.(ethyl1-methy1-carbamol) -4-t 4t trifluoromethyl-biphenyl-2-carbOnyl) -amino] -phenyl)acetoxyxnethyl)-2-phenyl-falonic acid diethyl. ester, (ethyl-methyl-carbafOyl)- 4 -trifluoromethylbiphenyl-2-CarbOlyl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, en (3-(ethyl-methyl-CarbafOYl) [(4'-trifluoromethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-acetiC acid 3, 3-biso 5 ethylcarbamOyl-3-PheflYl-Propyl ester, (piperidine-1-CarbonYl)- 4 -trifluoromethyl- 00 ci biphenyl-2-carbOlYl) -amino] -phenyl)-acetic acid 2, 2-biso ethylcarbamOyl-2-PhelYl-ethYl ester, 0 (3-(pyrrolidile-1-CarbOflYl)- 4 -trifluoromethylbiphenyl-2-CarbOlYl) -ami-no] -phenyl)'-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, (pyrrolidine-l1-carbonyl) -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl}-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, 3- (nethyl-propyl-carbamfOYl) -trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetic acid 2,2-bisethylcarbamoYl- 2-phenyl-ethyl ester, (rethyl-propyl-CarbaloyJ-) -trifluoromethylbiphenyl-2-CarbolYl) -amino] -phenyll-acetic acid 3 ,3-bisethylcarbafOyl- 3-phenyl-propyl ester, (3-dimethylcarbatOyl-4- -trifluoromethy-bphel- 2-carbonyl) -amino I-phenyl}-acetic acid 2-ethylcarbamoyl- 2-phenyl-ethyl ester, 2-phenyl-2- (pyrrolidine-1-CarbOnYl) trifluoromethyl-biPhel-2-carbonyl) -amino] -phenyl} acetoxymethyl)-falOfliC acid diethy. ester, 2-pheny1-2-(2-{3-(piperidifle-1-carbonYl)- 4 trifluoromethyl-biPhekyl-2-carbolYl) -amino] -phenyl)acetoxyniethyJl)-ma1onic acid diethy. ester, {3-dimethylcarbanoyl-4- r-trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2propionylamino-ethyl ester, {3-dimethylcarbanoyl-4- 4'-trifluoroniethyl-biphenyl- 2-carbonyl)-amino)-phenyl)-acetic acid 2-phenyl-2propionylamino-ethyl ester, 00 (3-dimethylcarbamoyl-4- -trifluoromethyl-biphenyl- 0' 2-carbonyl)-aminol-phenyl)-acetic acid 2-(2,5-dioxoo pyrrolidin-1-yl) -2-phenyl-ethyl ester, {3-dijmethylcarbamnoyl-4- -trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetic acid 2-ethylcarbamoylbenzyl ester, (3-dimethylcarbamoyl-4- -tritluorornethyl-biphenyl- 2-carbonyl)-aiino] -phenyll-acetic acid 2ethylcarbainoylmethyl-benzyl ester, (3-dimethylcarbanoyl-4- -trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetic acid 2-isopropylamino-2phenyl-ethyl ester hydrochloride, [3-dirnethylcarbamoyl- 4-(2 -trifluorornethylbenzoylamino) -phenyl] -acetic acid 2, 2-bis-ethylcarbamoyl-2phenyl-ethyl ester, 2- [3 -dimethylcarbamoyl- 4- trifluotcomethylbenzoylamino) -phenyl] -acetoxymethyl)-2-phenyl-malonic acid diethyl ester, 2- (2-(3-direthylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2phenyl-malonic acid diethyl ester, 2- (2-f 3-dimethylcarbamoyl-4- '-fluoro-biphenyl-2carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-J4- [(4--bromo-biphel-2-carbol) -ain-fo)-3en dirnethylcarbanoyl-pheflyl) -acetoxymethyl) -2-phenyl-malonic acid diethyl ester, o 5 3-dirnethylcarbaxnoyl- 4-1(4' -trifluoromethyJ--biphenyl- 2 -carbonyl) -amino] -phenyl)kacetic acid 2-acetylamino-2- 00 phenyl-ethyl ester, 0' (3-dimethylcarbamoyl-4- -trifluoromethyl-bipheyl- 0 2-carbonyl) -amino] -phenyl)-acetic acid 2-butyrylainro-2phenyl-ethyl ester, (2-benzoyl-belzoylafilO)-3-dimethylcarbamoylphenyl] -acetic acid 2 ,2-bis-ethylcarbainoyl-2-pheflyl-ethyl ester, (2-benzoyl-benzoy8fiflO)-3-di~flethYlcarbalYphenyl]-acetoxylethyl-2-PhelyiflalOflic acid di!ethyl ester, 2- (2-{3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl}-acetox-ymethyl) -2phenyl-malonic acid dirnethyl ester, 2-cyclopentyl-2-C2-(3-dimlethylcarbamol-4-(4' trifluoronetby1-bipheny-2-CrbOlYl) -amino) -phenyl)-acetoxy methyl)-malonic acid diethyl ester, 2-cyclohexyl-2-(2-{3-dimethylc-rbamOyl 4 t trifluoromethyl-biphenyl-2-carbOlyl) -amino] -phenyl)- acetoxy methyl)-malonic acid diethyl aster, 2-(2-{4-[(4'-chloro-biphel-2-carbofl)-amiflL3diinethylcarbanoyl-phel}-acetoxyrnethyl) -2-phenyl-m&lonic acid diethyl ester, 2-(2--{4-[(4'-acetyl-biphenyl-2-carboflyl)-liflol-3dimethylcarbamoyl-pheny-}-acetoxymethyl) -2-phenyl-malonic acid diethyl'ester, [3-dimet~ylcarbamO yl-4- (2-phenoxy-belzOylaiflO) Ct phenyl] -acetic acid 2, 2-bis-ethylcarbamnOYb-2-PheflYl-ethYl ester, 2-{2[-iehlcrol4(2- eox-enolaiophenyl1-acetoxymethyl}-2-phel-malofliC acid diethyl ester, 00 o ~diniethylcarbamOyl-pheflYl)-aCetOXYmfethYI) -2-phenyl-malOfliC ci acid diethyl ester, 2-(2-(3-dimethylcarbafloyl-4-[(4-mfethYl- 4 trif luoromethyl-biphelyl-2-CabolYl) -amino) -phenyl)acetoxymethyl)-2-phel-maOfliC acid diethyl ester, 2-(2-{3-dimethylCarbaBoyl-4-[ (5-methyl-4 trifluoromethyl-biphelYl-2-C'bOlYl) -amino] -phenyl) acetoxymethyl)-2-PhelYl-JalOflic acid diethyl. ester, {3-dimethylcarbamOyl-4- -trifluoromethyl-biphel- 2-carbonyl) -amino]-phenyl)-acetiC acid 2methanesulfonylamilo- 2-phenyl-ethyl ester, 3-(2-{3-dimethylcarbaflOyl-4-[ -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyijk-acetoxy) -2-phenylpropionic acid ethyl ester, {3-dimethylcarbamoyl-4- -trifluoromethyl-biPhelyl- 2-carbonyl) -amino] -phenyl)-acetic acid 2- (methyl-propionylamino) -2-phenyl-ethyl ester, 2- (2-{3-diznethylcarbamoyl-4- -trifinoromethylbiphenyl-2-carbonyl) -amino) -phenyl)-acetoxy) -propyl] -2phenyl-malolic acid diethyl ester, 2-(2-{3-dimethylcarbaROYl-4-[ (5-methoxy-4'trifluoromethyl-biphenyl2-CarbOlYl)-amino] -phenyl)acetoxymethyl)-2-PhelYl-falOlic acid diethyl ester, (5-chloro-4' -trifluorOmfethY1-biPhel-2en carbonyl) -amino] -3-dimethycarbamfl-Phefl)acetoxymethyl) -2 -phenyl-maloflic acid diethyl ester, .2 7 (2-{3-dimfethy1carbamoy-4[(6-methYl- 4 trifluoromethyl-biPhelYl-2-CarbOlYl) -amino] -phenyl)- 00 ci acetoxynethyl)-2-PhelYl-falOfliC acid diethyl ester) o- 2(~3-disnethy1Car bafl- 4 -trifluoromethyl- 0 ~biphenyl-2-carbOlYl) -amino] -phenyll-acetoxymfethYl) -2phenyl-malonic acid di-2, 2.2-trifluoroethyl ester, 2-(2-{3-dimethy1carbamoy1-4-[(2'-fluoro- 4 trif luoromethYl-biphel-2-car bonyl) -amino] -]phenyl) acetoxymethyl)-2-Phelyl-maloliC acid diethyl ester, 2 -diethy1CarbamOY1> 2-f lUorO- 4 trifluoromethYi--biPhelyl-2-carbolYl) -amino] -phenyl)acetoxymethyl)-2-PhenYl-malOnic acid diethyl ester,- 2-2(-rm--imthlabmy--(trifluoromethYl-biPhenYl 2 -carbonyl) -amino] -phenyl) acetoxymethy)-2-PhenYPlflalOfliC acid diethyl ester, 2-(2-{3-chloro-5-di-1ethylcrbamoy1-4-( 4 trif luoromethyl bphel l- 2-carbonlyl) amino -phenyl) acetoxymethyl)-2-PhenYl-maloniC acid diethyl ester, 2-(2-{3-dirnethylCarbBahoyl-4- -fluoro-4 trifluoromethYl-biPhel-2-carbonyl) -amino] -phenyl) acetoxymethy.)-2-PhelYl-faloniC acid diethyl ester, 2 -(2-{4-[(3'-chloro-4'trif1uoromethy1-biphenyl- 2 carbonyl) -amino] -3 -dimethylcarbanOyl-PhelYl) acetoxymethyl)-2-phenYl-malOfliC acid diethyl ester, 2- {3-dimethylcarbaloyl-4- '-trifluoromethylbiphenyl-2-carbolyl) -amino] -phenyll-acetOxylfethyl) nitro-pyridin-2-y)-malOliC acid diethyl ester, -trifluoromethy-biphel--2-CarbOlYl) -amino] -phenyl)o 5 acetoxyrnethyl)-malolic acid diethyl ester, (2-{3-diiethylcarbafOyl-4- -trifluoroinethyl- 00 ci biphenyl-2-carbol) -amino] -phenyl)-acetoylfethYl) -2o pyridin-2-yl-malonic acid diethyl ester, 0 2f-hor--iehycraol -loo4[(4' trifluoromethyl-biphenyl-2-CarbOflYl) -amino] -phenyl)acetoxymethyl)-2-phelyl-malOlic acid diethyl ester, 2-2(-rm--iehlcraol2fur--(4' trifluoromethyl-biphenyl-2-OarbOlYl) -amino) -phenyl)acetoxymethyl)-2-phenyl-falOfliC acid diethyl ester, 2- (2-f 3-dimethylcarbanoy-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetoyfetbYl) -2-otolyl-malonic acid diethyl ester, 2- 2-{3-dimethylcarbafoyl -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxynethYl) -2-rntolyl-malonic acid diethyl ester, 2- (2-{3-dirnethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetOxynethyl) -2-ptolyl-malonic acid diethyl ester, 2-2clr-hnl--2(-iehlabmy--(1 trifluoromethyl-biphenyl-2-carbOnYl) -amino] -phenyl)acetoxyrnethyl)-naloniC acid diethyl. ester, 2-3clr-hnl--2(-iehlabmy--(1 trifluoromethyl-biphenyl-2-carbOnyl) -amino] -phenyl)acetoxyznethyl)-malonic acid diethyl ester, trifluoromethyl-biphelyl-2-CarbOfl) -amino] -phenyl}en acetoxyniethyl)-rnaloniC acid diethyl ester, 2- (2-{3-dimethylcarbamOYl-4-[ -trifluoromethylo 5 biphenyl-2-carbonyl) -amino] -phenyl)-acetoxyfethyl) -2phenyl-succiflic acid diethyl ester, 00 2- (2-f 3-dimethylcarbamoyl-4- -trifluotromethylo) biphenyl-2-carbOlyl) -amino] -phenyl}-acetoxymethyl) (2- 0 znmethoxy-phenyl)-malOlic acid diethyl. ester, 2- (2-{3-dimethylcarbaflOYl-4-[ -trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetoxymethy-)-2- (3methoxy-phenyl)-malolic acid diethyl ester, 2- (2-(3-dimethylcarbamoYl-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -pheny1)-acetoxynethyl) (4methoxy-phenyl)-malonic acid diethyl ester, 2-(2-{4-[(5,4'-bis-trifluorOWethY1-biPheflyl-2carbonyl) -amino] -3-dimethyJlcarbamoyl-phel)acetoxymethyl)-2-phenyl-a-ofliC acid diethyl ester, 2-C [(6-chloro-4' -trifluoromethyl-biphelyl-2carbonyl) -amino] -3-dimethylcarbanoyJl-phenYl} acetoxyniethyl)-2-phenyl-malolic acid diethyl ester, 2- (2-f W*-dimethylcarbanoyl-4- [(6-fluoro-4' trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl} acetoxyiethyl)-2-pheyl-faOliC acid diethyl ester, 2-[2-(2-{3-dimethylcarbamoyl-4-[(5-mfethYl-4'trifluoromethyl-biphelYl-2-carbolYl) -amino] -phenyll acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2-(2-(3-dimethylcarbamloYl-4-[ (5-ethoxy-4'trifluoromethyl-biphenyl-2-Carboflyl) -amino] -phenyl)acetoxynethy)-2-pheny1-m.lOfiC acid diethyl ester, 2-C2-{3-dimethylcarbaml-4-[(5-isoprO oxCy- 4 en trifluoromethyl-biphenyl-2-carbODYl) -amino] -phenyl)acetoxymethyl) -2-pheknyJl-ra1OniC acid diethyl ester, carbonyl) -amino) -3-dimethylcarbamOyl-phflYll -acetc'xy) 00 ci ethyl]-2-phenyl-maloliC acid diethyl ester, o 2-(2-{3-dimethylcarbamoly-4-[(6methoxy- 4 0 trifluoromethyl-biphenyl-2-CarbolYl) -amino] -phenyll acetoxymethyl)-2-phenyl-malOrliC acid diethyl* ester, 2-C 2-{3-dimethylcarbafOyl-4- [(3-methyl-4' trifluoromethyl-biphenyl- 2-carbonyl) -amino]I-phenyl) acetoxymethyl)-2-phelyl-malOfliC acid diethyl ester, 2-12- 2,4-bis-trifuoromethy-belZOYaUfO) -3dimethylcarbamoyl-phelyl) -acetoxymethy}-2-Phel-malolic acid diethyl ester, 2-C 2-{3-dimethylcarbamoyl-4- -methyl-bi-phenyl-2carbonyl) -amino] -phenyl) -acetoxymethyl) -2 -phenyl-malonic acid diethyl ester, 2-ethy1-4-triuoromfethY1-belzoylafilO) -phenyl] acetoxynethy)-2- phenyl -malonic acid diethyl ester, 2-(2-{3-dimethylcarbamoyl-4-[(4' -ethyl-biphenyi-2carbonyl) -amino] -phenyl }-acetoxymethyl) -2 -phenyl-malonic acid diethyl ester, 2-(2-{3-dimethylcarbanoyl-4-[C 4 '-isopropenylbiphenyl-2-carbOlyl) -amino] -phenyll-acetoxyfethYl) -2phenyl-mnalonic acid diethyl ester, 2- (2-{3-dimethylcarbafoyl-4- T-isopropyl-biphenyl- 2-carbonyl) -axninoj -phenyl)-acetoymethYl) -2-phenyl-malonic acid diethyl ester.

2-{2-[3-imethylcarbwmoy1-4-(2-isopropefl- 4 trifluorcmethyl-benzoylailO) -phenyl]I -acetoxyrnethyl)1-2phenyl-malonic acid diethyl ester, o 2-{2-[3-dimethylcarbamofl-4-(2-isopropyl- 4 trifluoromethyl-belZOYlalilO) -phenyl] -acetoxymethyl} -2- 00 ci phenyl-inalonic acid diethyl ester, o ~2-(2-{3-diethylcarb1l-4- (3-trifluorornethyl- 0 ~phenylamino) -benzoylanino] -phenyl )-acetoxymethyl) phenylmalonic acid diethyl. ester, 2-f 2-I3-dixnethylcarbaloyl-4- -trifluoroiethybiphenyl-2-carbOllOXY)-phenyl] -acetoxymethyll-2-phelylmalonic acid diethyl ester, 2-{3-dimethylcarbamOyl-4- (3-trifluoromethylphenoxy) -benzoylamino] -phenyll-acetoxymethYl) -2-phenylnialonic acid diethyl ester, f3-dimethylcarbauoyl-4- -trifluoromethyl-biphelyl- 2-carbonyl)-amiflO]-phenyl)-acetic acid 2-ethyl-2-phenylbutyl ester, 2-{3-dimethylcarbamOYl-4- [2-C 4-trifluoromethylS phenoxy) -benzoylamino] -phienyll -acetoxymethyl) -2 -phenyl.inalonic acid diethyl ester, f3-dimethylcarbanOyl-4- -trifluorornethyl-biphenyl- 2 -carbonyl) -amino] -phenyl }-acetic acid 1 -phenylcyclopropylmethyl ester, f3-dirnethylcarbainOYl-4- [(41 -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl}-acetic acid 2 ,2-diphenyl-ethyl ester, f3-clirethylcarbamofly-4- -trifluoromethyl-biphelYl- 2-carbonyl) -amino]I -phenyl)j-acetic acid 1-phenylcyclopentylmethyl ester, M {3-dirnethylcarbamoyl-4- '-trifluoromethyl-biphefl 2-carbonyl) -amino] -phenyl)-acetic acid 3-hydroxy-2o 5 hydroxymethyl-2-phenyll-PrOPYl ester, 3-dimethyCarbamflY-4- -trifluoroflthy1-biphel1 00 2-carbonyl) -amino] -phenyl)-acetic acid 3-acetoxy-2oacetoxymethy1-2-pheny- prOPYJ ester, 0 2-f 3-dimethylcarbaxnOyl-4-[(4' -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl}-acetOxYmfethYl) -2thiophen-2-yl-ma-OfliC acid diethyl ester, 2- (2-{3-dimethylcarbamoyl-4-.[ (4'-trifluorornethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetOXymethY.) -2thiophen-3-yl-malolic acid diethyl ester, 2-(4-dimethylcarbamlf -54 -trifluoromethylbiphenyl-2-carbonyl) -amino.] -pyri-din-2-yJl)-aCetOX-YmethY1) -2phenyl-malonic acid diethyl ester, 2-{3-dimethylcarbafoyl-4- 1(4' -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)'aetoxymfethYl) (3methyl-thiLophen-2-y)-mlolic acid diethyl ester, 2- (2-f 3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carboiy l) -amino] -phenyl}-acetoxymfethYl) methyl-thiophen-2-y1) -ialonic acid diethyl ester, 2- (2-{3-dimethylcarbaxnOyl-4- -trifluoroinethylbiphenyl-2-carbolyl) -amino] -phenyl)-acetoxyImethYl.)-2thiazol-2-yl-malOfliC acid diethyl ester, 2-f 3-dimethylcarbamnoYl-4- -trifluoroinethylbiphenyl-2-carbolyl) -amino] -phenyl)-acetOxyfethYl) -2isopropyl-malonic acid diethyl ester, trifluoromethyl-biphelyl-2- carbonyl) -amino] -phenyl)}en acetoxymethyl)-malofliC acid diethyl ester, 2- (2-{3-dimethylcarbamoYl-4-[ -trifluoromethylo 5 biphenyl-2-carbOflYl) -amino] -phenyl)-acetOxymhethYl) -2iLsobutyl-malonic acid diethyl ester, 00 2- (2-{3-dimethylcarbafoyl-4- -trifluoromethyo biphenyl-2-carbonyl) -amino) -phenyl)-acetOxymethyl) -2- 0 propyl-malonic acid diethyl ester, 2-,(2-{3-diinethylcarbalnoyl-4-[ -trifluoromethylbiphenyl- 2-carbonyl) -amino] -phenyl) -acetox-ymethyl) -2 -ethylmalonic acid diethyl ester, 2-butyl-2-(2-{3-diTfethYlcarbaloykL4[( 4 trifluoromethyl-biphenyl- 2-carbonyl) -amino) -phenyll acetoxymethyl)-rnaloniC acid diethyl ester, 2-allyl-2-(2-(3-dimethylcarbmOYl- 4 4 trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl) acetoxymethyl)-malonic acid diethyl ester, 3- (2-{3-dirnethylcarbalnoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxy) 2-bisethoxycarbonyl-prOpioflic acid ethyl ester, 2- (2-{3-dimethylcarbanoYl-4-[ -trifluoromethylbiphenyl-2-carbOr'yl) -amino] -phenyl)-acetoxynethyl) (1methyl-butyl)-malOniC acid diethyl ester, 2-(2-{3-ethoxy-4-[ (4'-trifluoromethyl-biphenyl-2carbonyl) -aminol -phenyl}-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, {3-hydroxy-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyl}-acetic acid 2, 2-bis-ethylcarbamoyl- 2-phenyl-ethyl ester, {3-methoxy-4- -trifluoromethyl-biPhel-l 2 en carbonyl) -amino] -phenyl}-acetic acid 2, 2-biLs-ethylcarbamoyl- 2-phenyl-ethyl ester, o 5 2-(2,-{3-methoxy-4-[ (4'-trifluoromethy1-biphenfl-2carbonyl) -amino] -phenyl}-acetoxynethyl) -2-phenyl-malonic 00 acid diethyl ester, o' {3-methoxy-4- -trifluorornethYl-bipheflYl- 2 0 carbonyl)-axnino)-pheflyl}-aCetiC acid 2-phenyl-2,2-bispropylcarbainoyl-ethyl ester, (3-methoxy-4- -trifluoromethy1-biPhel-2car~bonyl) -amino] -phenyl)-acetic acid 3, 3-bis-ethylcarbamoyl- 3-phenyl-propyl ester,, {3-etboxy-4- [(41 -trifluoromethyJ-biPhefylY>> carbonyl) -amino] -pheny1)-acetic acid 2, 2-bis-ethylcarbamnoyl- 2-phenyl-ethyl ester, {3-ethoxy-4- -trifluoromethy1-biPhe1Y1-2carbonyl) -amino] -phenyl)-acetic acid 3, 3-bis-ethylcarbamoyl- 3-phenyl-propyl ester, 2- (2-{3-isopropoxy-4- -trifluoromethyl-biphenyl-2carbonyl) -amino] -phenyl)-acetoxynethyl) -2-phenyl-malonic acid diethyl ester, {3-isopropoxy-4- [(41 -trifluoromethy-biphel-2carbonyl) amino) -phenyl)}-acetic acid?2, -bis -ethylcarbamoyl 2-phenyl-ethyl ester, {3-isopropoxy-4- -trifluoromethyl-biPhenYl-2carbonyl) -amino] -phenyl}-acetic acid 3, 3-bis-ethylcarbamoyl- 3-phenyl-propy. ester, {3-propoxy-4- -trifJluoromethy1-biPhenYJl-2carbonyl) -amino) -phenyl) -acetic acid 2 ,2-bis-ethylCrbafOyl- 52-phenyl-etbyl ester, en ((3-benzyloxy -rifluo rohY1bihelY12hn carbonyl) -amino] -phenylil-acetic acid 2 ,2-isehyl-ralOyL o 5 2-phenylethyl ester, 2- (2-{3-beyoxy-4- trifuoronethy-biphefl-2- -amino] -pheny1I1-aCetOXYmfethYl) -2-pheny1-mal1onic 0 acid diethyl ester, 0 -trifJluoronmethy1-biPheylY-2carbonyl) -io pheny)-actxetO~thYl) -2-phenyl-malofic ai acdiethyl ester, 2-2-[methoxyin-4-(4' trifuoromethY-biPheY1-2carbonylox)ai -phenyl acetynty}2Pellalfic acid 22bsehlaraol dihelethyl ester, {13-dimehyi-ll-4- -trifuoromethy-biPhel-2carbonyl) amino]I -phenyl)F- acetic acid 2, 2 -bis -ethylcarbanoyl 2-phenyl-ethyl ester, {3 -piprioldin-1-yl-4- -trifluoromethyl-bipheflyl>2 carbonyl) amino] -phenyl) -acetic acid 2, 2 -bis -ethylcarbamoyl 2-phenyl-ethyl ester, {-peyrli2(-3pdin-1-yl-4-[[4(4rfloomt'-bhel2 trifluoromethyl -biphenyl- 2-carbonyl) -amino] -phenyl) acetoxymethyl)-malOlic acid diethyl ester, 2-phenyl-2- (2-{3-pyrro2-idifl-1-YI- 4 trifluoromethyl-biPhelyl-2-carbolYl) -amino] -phenyl)acetoxymethyl)-malonic acid diethyl ester, 43 2- (2-{3-diznethylamilo'-4- -trifluoromethYl- -biphenyl-2-CarbOl.) -amino] -phenyl}-acetOXYmethYl) -2en phenyl-mal-onic acid diethyl ester, 2- (2-C3-Inorpholifl-4-yl-4- -trifluoromethyl-biphelY o 5 1-2-carbonyl) -amiLno] -phenyl)-acetOXylethYl) -2-phenylmalonic acid diethyl ester, 00 2- (2-{3-diethylamino-4- 1(4' -trifluoromethY1-biPhelo 2-carbonyl) -amninolI -phenyl}-acetOxyfethYl) -2-phenyl-malolic Ciacid diethyl ester, 2- (2-{2-methyl-3- -trifluoromethyl-biPhefll 2 carbonyl) -amino] -phenylil-acetoxy) -ethyl]I -2-phenyl-maloflic acid diethyl ester, 2-hnl2(-3[4-rfurmty-ihnl2 carbonyl) -amino] -phenyl}-acetoxyTethYl) -ialonic acid diethyl ester, 2-phenyl-2- 3- -trif luoromethyl-biPhelyl-2-, carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -malonic acid diethy-ester, {3 -trif luoromethyl-biphenyl-2-CarbOfYl) -ami-no] phenyl}-acetic acid 3, 3-bis-ethylca-rbamoyl-3-Phel--PrOPYl ester, -trifluoromethyl-biPheflYl-2-CBrbOnYl) -amiLno] phenyl)'-acetic acid 3-phenyl-3, 3-bis-propylcarbamolJ-PrOPYl ester, 2-2(-4mty--('trfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-ma -lonic acid diethyl ester,.

2- (2-{2-methyl-5- -trifluoromethYlrbiPheflYl-2carboflyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-ma-lonic acid diethyl ester, -trifluoromethYl-biPheflYl-2Cabonyl) -anilno] en phenyl}-acetic acid 3 ,3-tis-isopropylCarbamfl-3-PhelYlpropy. ester, o 5 {2-methyl-3- -trif luoromethyl-biphel- 2 carbonyl) -amino] -pheny..I-acetiC acid 3, 3-bis-ethylcarbanoyl- 00 3-phenyl-propy- ester,.

0' {2-rnethyl-3- -trifluoromethyl-biPhel2 0carbonyl) amino]I -phenyl) -acetic acid 4, 4 bis-ethylcarbanoyl 4-phenyl-bUty. ester, {2-methyl-3-[ -trifluorometlyl-biPheflyl- 2 carbonyl) -amino] -phenyl)}-acetic acid 3-phenyl-3. 3-bispropylcarbarnoyl-propyl ester,.

{2-methoxy-3- -trifluoromethyl-biphelyl- 2 carbonyl) amino] phenyl) -acetic acid 3, 3- bis -ethylcarbfloyl 3-phenyl-propyl ester, 2-[2-(2-{2-methoxy-3-L(4'-trifluorOmethYl-biphelYl- 2 carbonyl) -amino] -phenyll-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, {2-ethoxy-3-1t(4' -trifluoromethyl-bipheflyl-2carbonyl) -amino] -phenyl)-aceti-c acid 3, 3-bis-ethylcarbaioyl- 3-phenyl-propyl ester, 2-12- (2-{2-ethosy-3- -trifluoroniethyl-biPheflyl-2carbonyl) -amino] -phenyl)-acetoxy) -ethyl) -2-phenyl-nalolic acid diethyl ester, 2-[2-(2-{2-isopropoxy-3-[ (4'-trifluoromethylbiphenyl-2-carbolYl) -amino] -phenyl)-acetoxy) -ethyl) -2phenyl-malonic acid diethyl ester, 2-12- (2-f 2-methoxycarboflyl-3- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetoxy)-ethYl] -2phenyl-rnalonic acid diethyl ester, 2-2(-2ehx--ehl'-(1tilooehl biphenyl-2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2phenyl-malonic acid diethyl ester, 4- '-trifluoromethyl-biphenyl-2-CarbOrlYl) -amino] 00j '4 benzoic acid 2- (2,2 ,2-trifluoro-ethylcarbafoyl) -9h- S fluoren-9-ylI-ethyl ester, 4- -trifluoromethyl-biphenyl-2-CrbOlYl) -amino] benzoic acid 2- (9h-fluoren-9-yl) -ethyl ester., n-biphenyl-2-yl-terephthalamic acid 2-f9--(2,2,2trifluoro-ethylcarbamoyl) -9h-fluoren-9-yl 1-ethyl ester, 4- -trifluoromethyl-biphenyl-2-carbolyl) -amino] benzoic acid 2- [(biphenyl-2-carbonyl)-ain~o]-ethyl ester, 4- -trifluoromethyl-biphenyl-2-CarbolYl) -amino] benzoic acid 2- 2-biphenyl-2-yl-acetylamiflo)-ethyl ester, 4-11(4' -trifluoromethyl-biphenyl-2-carbolYl) -amino] benzoic acid 3-naphthalen-.1-yl-3-(2,2,2-triflUOroethylcarbaloyl) -propyl ester, 4-f -trifluoromethyl-biphelyl-2-carbolyl) -amino] benzoic acid 3- (2,2 ,2-trifluoro-ethylcarbafoyl) naphthalen-1-yl] -propyl ester, 4- -trifluoromethyl-biphenyl-2-carbolyl) -amino]benzoic acid 3,3-diphenyl-3-(2,2,2-triflUOroethylcarbaznoyl)-propyl ester, 4-f -trifluoromethyl-biphenyl-2-CarbolYl) -amino] benzoic acid 3-biphenyl-2-y1-3;.-(2,2,2-triflUOroethylcarbamoyl) -propyl ester, 4- -trifluorornethyl-biphenyl-2-carbonyl) -amino] benzoic acid 3-phenyl-3- 2-trifluoro-ethylCarbamOyl) propyl ester, en 4-f -trifluoromethyl-biPheflYl-2-CarbOnYl) -amino] benzoic acid 2- 2-trifluoro-ethylcarbafOyl) o 5 naphthalen-2-y-]-ethyl ester, 4- "-trifluoromethyl-biphenyl-2-CarbOlYl) -amino] 00 benzoic acid 3-(2,6-dichloro-phenyl)-3-(2,2.2-triflUOrOo ethylcarbanoyl)-ptfOPYl ester, 0 -trifluoromethyl-biphenyl-2-CarbOflYl) -amino] benzoic acid 3-(2-chloro-pheny1)-3-(2,2,2-trif1UOrOethylcarbamoyl) -propyl ester, 2-phenyl-2-(2-{4-1(4'-trifluoromelthyl-biphefl- 2 carbonyl) -amino] -benzoyloxy) -ethyl) -ralonic acid diethyl ester, 2- (2-{3-methyl-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -benzoyloxy) -ethyl) -2-phenyl-malonic acid diethyl ester, 2-(-2-(2chloro-4-I(4'-trifluoromfethYl-biphelYl-2carbonyl) -amino] -benzoyloxy)-ethyl) -2-phenyl-malonic acid diethyl ester, 2-hnl2f-4(1tifurmty-ihnl2 carbonyloxy) -benzoyloxy] -ethtJ.1-malonic acid diethyl ester, .2f-4(-ezy-ezyoy-ezyoy-ty)2 phenyl-maloflic acid diethyl ester, 4- -trifluoromethy--biphelyl-2-carbOlYl) -amino] benzoic acid 3, 3-bis-ethylcarbamoyl-3-phelyl-Propyl ester, 4'-trifluoromethyl-bipheflyl-2-Carboxylic acid 4- 3-bis-ethylcarbamoyl-3-phelyl-propoxycarboflYl) -2chioro-phelyl ester, 4t' trifluoromethy1-biPhefli2-carbOxcylic acid 4- 3-bis-ethy1CarbafolOY13-PheflPropo2CYcarbonYl) -phenyl en ester, trifluoroxnethyl-biPheflYl- 2-carboxyliC acid 4-(3 ,3-i-tycabmy--pey-rpoyabn -2,6dichioro-phelyl ester, 00 4-rnethyl-4- -trifluoromnethyl-biPhenfl- 2 -Carbon~Yl) o amino] -cyclobexanecarboxylic acid 2-19- 2-trifluoro- 0 ethylcarbanOyl) -9h-fluoren-9-yl] -ethyl ester, 4- -trifluoromethyl-biphelyl-2-CarbOflYl) -amino) cyclohexanecarboxylic acid 2- 2-trifluoroethylcarbafoyl) -9h-fluoren-9-y-] -ethyl ester, trifluoromethyl-biphelyl-2-carbOlYl) -ami-no) cyclohexaneCarboxylic acid 3-phenyl-3-(2, 2, 2-trifluoroethylcarbamOyl)-PrOPYl ester, 2-phenyl-2-(4- -trifluoromethyl-biPheflYl- 2 carbony-) -amino) -cyclohexanecarbonyoxymfethYl)ffialOnic acid diethyl ester, 2-phenyl-2-(2-{4-[ -trifluoromethyl-biphefl2carbonyl) -amino] .cyclohexanecarboflylOxy)-ethyl) -malonic acid diethyl ester, 2-phenyl-2-(2-{4-[ -trifluoromethyl-biPheflYl-2carbonyl) -amino] -piperidin-i-yi}-acetoxymethyl) -malonic acid diethyli ester.

2-phenyl-2-(2-{4-[ -trifluoromethyl-biPheflYl- 2 carbonyl) -amino) -indol-1-yl}-acetOxYflethYl) -malonic acid diethyl ester, 2- (2-{2-niethyl-4- 1(4' -trifluoromethyl-biPhefl2carbonyl) -amino] -benzoimidazol-1-Yl}-acetOXrmethYl) -2- 48 phenyl-maloflic acid diethyl. ester, [2-oxo-3- -trifluoromethyl-biPhefylY1>carbonYl)' en 2,3-dihydrO-beflzooxaZOl6yllacetic acid 2,2-bisethylcarbamfl-2-PheflYl-ethrl ester, o 5 2- (2-{3-ethoxycarbolYl-4-[(4' -trifluoromethYl- 00 biphenyl-2-CarbOlYl) -amino] -phenyl)-aCetOXYmethYl) -2phenyl-malolic acid diethyl ester, o (3-.{3-dimethylCarbamfoYl- 4 -trifluorOmfethyl- 0 ~biphenyl-2-CarbOlYl) -amino] -phenyl-prOPiOlOXYmethYl) -2phenyl-malolic acid diethyl ester, -tritluoromethyl-bipheyl-l2-carbonYl) -amrifO] methyl}-benzO-ic acid 2, 2 -bis -ethylcarbamOYl -2 -Phefll-ethyl ester, -trifluoromethyl-biphefyll2-carbonYl) amino] -phenylll-prOpioflic acid ethylcarbamoyl-PhelYl-lethyl ester, (2,2-i-tycr my--hnletoyabnl methyl) -trifluoromethyl-biPbeflYl-2-CarbonYl) -amino] benzoic acid benzyl ester.

2 -bis-ethylCarb8IfOyl-2-Phel-lethoxcycarbonYlmethyl) -trifluoromethy-biPhelyl-2-CarbolYl) -amino] benzoic acid, 2-bis-ethylcarbamfl-l2-Phefyl-thO2YCabonYl> methyl) [(4'-tilooety-ihnl -abnl-amino] benzoic. acid ethyl ester, 2-pheflyl-2-(2-(4-[ -trifluoromethy1-biphefyl>2 carbonyl) -amino] -benzoimidazOl-1-Y>aCtO2CYIethYl) -malonic -acid diethyl. ester, -trjfJuorornethyl-biphefyl2-Carboflyl) -am~inol xnethylj-benzoic acid 3. 3-bis-ethylcarbamoflJ-3-PheflI-PrOPYl ester, -tycramy--hnletoyabnl methyl) -trifluoromethyl-biphenyl-2-CarbOflYl) -amino) benzoic acid methyl ester, 2- (2-{3-benzyloxycarbOfl4 -trifluoromethyl- 00 biphenyl-2-carbolYl) -amino] -phenyll-acetoxymethyl) -2o phenyl-malonic acid diethyl ester, carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-(2-[2-oxo-3-(4'-trifluoromlethyl-biPhel- 2-carbonyl) -2 ,3-dihydro-benzooxazol-6-yl] -acetoxymethyl)-2phenyl-malonic acid diethyl ester, 2-2[-x--4-rfurmty-ihnl2 cabnl--z-lyl[..0ot-()24tin3y] acetoxymethyl)-2-phenyl-nalOliC acid diethyl ester, 2- (2-{3-isopropoxycarbonyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxynethyl) -2phenyl-malonic. acid diethyl ester, 2- (2-{3-methoxycarbOnyl-4-[ -trifluoromethylbiphenyl-2-carbolyl) -amino] -phenyl)-acetoxynethyl) -2phenyl-malonic acid diethyl ester, 2.-[2-(3-dinethylcarbamoyl-4-{[1-(2-flitrol-4-trifluoromethyl-phenyl) -pyrroli-dine- 2 -carbonyl ]-amino) -phenyl) acetoxymethyl] -2-phenyl-malonic acid diethyl ester, 2- (2-{3-acetylamino-4- -trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetoxynethyl) -2-phenyl-rualonic acid diethyl ester, 2- (2-f 3-methoxYcarbonylaliflo- 4 114' -trifluoromethylbiphenyl- 2-carbOlyl) -amino II-phenyl) -acetoxymethyl) -2 -phenylen malonic acid diethyl ester, 2-(2-{3-(4-methyl-thiazol-2-Yl)4( 4 o 5 trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl) acetoxymethyl)-2-PhelYl-lalofliC acid diethyl ester, 00 2-hnl2(-6[4-rfurmty-ihnl2 o carbonyl) -amino] -biphenyl-3-yl}-aCetOX-YmethYl) -malonic acid Ci diethyl ester, carbonyl) -amino] -phenyl)-acetoxylethYl) -2-phenyl-malonic acid diethyl ester, 2- (2-f 3-dimethylaminofethyl-4 -trifluoroinethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetOxyfethYl) -2phenyl-malonic acid diethyl ester, 2- (2-f 3-(methoxy-mfethyl-carbamOYl) trifluoromethyl-biphelYl-2-CarbolYl) -amino] -phenyl)acetoxymethyl)-2-Phelyl-malOflic acid diethyl ester, .2-(2-{3-isobutyryl-4-[ (4'-trifluorOmethyl-biphelyl-2carbonyl) -amino] -phenyllj-acetox-ynethYl) -2-phenyl-malonic acid diethyl ester, and 2-(2-{3-(1-hydroxy-2-methYl-PrOPYl)- 4 trifluoromethyl-biphelYl-2 -carbonyl) -amino] -phenyl) -acetoxyi ethyl)-2-phenYl-l'alOniC acid diethyl ester; (23) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of 4- -trifluoromethyl-biphenyl-2-arbOrYl) -amino] phenyl)-acetic acid 2, 2-bis-ethylcarbamoyl-2-Phelylethyl ester, en 2-phenyl-2-{2-[4-E (4'-trifluorornethyl-bipheflyl- 2-carbonyloxy) -phenyll -acetoxymethyl)-maloliC acid diethyl o 5 ester, 2-(2-{3-methyl-4-[ (4'-trifluoromnethyl-biphefl 00 2-carbonyl) -amino] -phenyl}-acetoxymfethyl) -2-phenyl-malonic o acid diethyl ester, 0 [methyl- -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl) -acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 3-ethyl-4- -trifluoromethyl-biphelYl-2-CabOlYl) amino] -phenyl) -acetic acid 2, 2-bis- ethylcarbaxnoyl-2-pheflYlethyl ester, -trifluoromethyl-biphenyl-2-CarbOlYl) ami-no]-phenyll-acetic acid 9-(2,2,2-trifluoroethylcarbamoyl) -9h-fluoren-9-ylmethyl ester, -trifluoromethyl-biphelyl-2-CarbOlYl) amino] -phenyl)-propionic acid I9- 2-trifluoroethylcarbamoyl) -9h-fluoren-9-ylmfethyl ester, -trifluoromethyl-biphenyl-2-CarbOlyl) -amnino] phenyl)-acetic acid 2-phenyl-2-(2,2,2-triflUOrOethylcarbamoyl) -ethyl ester, 2-phenyl-2- -trifluoromethyl-bipheiyl-2carbonyl) -amino] -phenyl} -acetoxymethyl) -malonic acid diethyl ester, 2-phenyl-2- -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxyfethyl) -ialonic acid diisopropyl ester, -trifluoromethya-bipheny-2-carbonyl) -amino] phenyll-acetic acid 2-pheny1-2.2-bis-(2,2, 2-triflUOroenethylcarbaxnoyl)-ethYl ester, 2-phenyl-2-( -trifluoromethyl-biPhefl- 2-carbonyl) -amino] -pbenyl}-acetOXymlethyl) -ma'lonic acid dimethyl ester, 00 2-cycloperltyl-2- (2-f 4- -trifluoromethYl-biPhelYl- 0' 2-carbonyl) -amino] -phenyll-acetoxyfethYl) -malonic acid 0 diethyl ester, 2-hnl2(-4[4-rfurmty-ihnl 2-carbonyl) -amino) -phenyl)-acetOxylethyl) -malonic acid dicyclohexyl ester, -trifluoromethy-biphelyl-2-CarbOlYl) -amino] phenyll-acetic acid 2, 2-bis-cyclohexylCarbalOYl-2-Phelethyl ester, -trifluorornethy1-biphelYl-2-CarbOll) -amino] phenyl}-acetic acid 2-phenyl-2, 2-bis-phenylcarbamloylethyl ester, -trifluoromethyl-bipheflYl-2-CarbolYl) -amino] phenyl)-acetic acid 2, 2-bis-isopropylcarbafOyl-2-PhelYlethyl ester, 2-benzyl-2- -trifluoromfethyl-biphe)y1- 2-carbonyl) -amino] -phenyl-acetoxyfethyl-falOfliC acid diethyl ester, 2- (2-{2-methyl-4- -trifluoromethyl-biphenYl- 2-carbonyl) -amino] -pheny1}-acetoxymethYl-2-PhelmalofliC acid diethyl ester, 4' -trifluoromethyl-biphelyl-2-CarboxCYliC acid 4- [2- .phenyl-2 ,2-bis- 2-trifluoro-ethycarba l) ethoxycarbolmfethYl] -phenyl ester, biphenyl-2-carbOXYliC acid 4-[2-phenyl-2,2-bis- (2,2,2 -trifluoro-8thYlearbamoyl) -ethoxycarbonylfeth-yl] phenyl ester, o 2-cyclohexyl-2-(2'-{ 4 4 (4'-trifluOrometbyl-biphefl 00 2-carbonyl) -amino] -phenyll-aCetOXYmfethYl) -malonic acid c-i diethyl ester, o 11~4- t(biphenyl-2-carbOl) -amino] -phenyll-acetiC acid Ci 2-phenyl-2, 2-bis- 2-trifluoro-ethYlCarbThOYl) -ethyl ester, 2-phenyl-2- (2-{2-trifluoromethYl-4 1(4'trifluorornethyl-biPhelYl- 2-carbonyl) -amino] -phenyl} acetoxymethYl)-falOflic acid diethyl ester, -trifluoromethY1-biPhefl2-carbonYl) -wninol phenyll-acetiC acid 2, 2-bis-methylcarbXfoYl-2-PheflYlethyl ester.

2-pyridifl-2-yl- 2 -trifluoromethylbiphenyl- 2-carbonyl) -amino] -phenyl) -acetoxytethyl-mfaloflic acid diethyl ester, 2-pyridin-3-yl-2-(2-( 4 K (4 -trifluorornethylbiphenyl-2-carboiyl) -amino] -phenyll-acetoxymethyl) malonic acid diethyl ester.

4' -trifluoromethyl-biphelYl-2-carbox i±c acid 4-(2 .2bis -ethylcarbamoYl- 2 pheny1-ethOXYcarbOlmlthYl) -phenyl ester, 2-hnl2(-3tiloomty--('tiloo rethyl-biphenYl-2-carbonYl) -amino] -phenyl) acetoxymethyl)-malOlic acid diethyl ester.

(4-11(4' -trifluoromethy1-biphelyl-2-CarbOflYl) -amino] phenyl)- acetic acid 2, 2 bis -buty1CactbaflY2 -phenl>ethyl ester, {3-methyl-4- -trifluorometbyl-biphenfl-l 2 carbonyl) -amino] -phenyl)-acetic acid 2.2-bis-ethyloarbamOY1o 5 2-phenyl-ethyl ester, 00 ci phenyl)-acetoxymethyl) -2-phenyl-maloflic acid diethyl ester, ci phenyl}- acetoxymethyl-2-Phel-malOflic acid diethyl ester, -trifluoromethy-biphel-2-carbOfll-8ThinOl phenyl)-acetic acid 3, 3-bis-ethy1CarbamOY1-3-pheflYl-PrOFYl ester, -trifluoromethy-biphel-2-carbOfll-mil]phenyl)-acetic acid 3-phenyl-3, 3-bis-propylcarbafOyl-PrOPY1 ester, [(biphenyl-2-carbonyl) -amino) -phenyl) -acetic acid 2, 2-bis-ethylcarbamnoy1-2-phenfl-ethYl ester, 2-phenyl-2-(2-14-( 3 -trifluoromethy1-biPhefl-2carbonyl) -amino) -phenyll-acetoxynethyl) -malonic acid diethyl ester., 4' -trifluoromethy1-biphenfl-2-CarbOXYliC acid 4- (2,2bi-tycraol2peylehxcro lehl-2chioro-phenyl ester, 2-(2-{4-[iSOprOpyl-(4' -trifluoromethylbiphenyl-2-carboyl-ailo] -phenyi}-acetoxyiethyl) -2phenyl-malonic acid diethyl ester, Lcyclohexyl- -trifluoromethyl-biPhenYl-2carbonyl) -amino] -phenyl}-acetoxymethYl) -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-{4-[ (4 -trifluoromethy-biphenyJ-2carbonyl) -amino] -phenyl}-acetorynethyl) -malonic aciLd en dipropyl ester, 2-phenyl-2- -trifluorornethyl-bipheflyl-2o 5 carbonyl) -amino] -phenyl}-acetoxynethyl) -malonic acid *diisobutyl ester, 00 -trifluoromethyl-biphflyl-2-CarbOl -amil]ophenyl}-acetic acid 2, 2-bis-isobutylcarbamoyl-2-PheflYl- Ci ethyl ester, -tritluoromethyl-biphenyl-2-Carbol -alilphenyl)-acetic acid 2. 2-bis-(3-nlethyl-butylcarbamOYl-2phenyl-ethyl ester, 2- (244- [ethyl- -trifluoroxnethyl-biphenyl-2carbonyl) -amino] -phenyl) -acetoxyrnethyl) -2-phenyl-malonic acid diethyl ester, 4- (4'-chloro-biphenyl-2-carbOlYl)-amifloI-Phefl)acetic acid 2 ,2-bis-(ethylcarbamoyl-2-pheflyl-ethyl ester, ,4'-dichloro-biphenyl-2-carbOnyl)-ailo]phenyl)-acetic acid 2, 2 -bi-s- (ethylcarbanoyl 2-phenyl -ethyl ester, {3-znethyl-4- -trifluoromethyl-biphenyl-2carbonyl}-aminO)-pheflyl}-aCetic acid 2-phenyl-2,2-bispropylcarbamoyl-ethyl ester, 4-1(4' -trifluoromethyl-biphenyl-2-CarbOnl)amino] -phenyl)-acetic acid 2 ,2-bis- (2-methoxyethylcarbanoyl) -2-phenyl-ethyl ester, 2-(2-{3-ethyl-4-[ (4'-trifluorornethyl-bipheflyl-2carbonyl)-amino] -phenyl)-acetoxymethyl) -2-phenyl-inalonic acid diethyl ester, {3-isopropyl-4- -trifluoromethyl-bipheflYl-2- C) carbonyll-amino] -phenyl)-acetic acid 2, 2-bisen ethylcarbamoyl-2 -phenyl-ethyl ester, Ni 2- (2-{3-isopropyl-4- -trifluoromethyl-biPhelyl-2o 5 carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic acid diethyl. ester, 00 {3-ethyl-4- -trifluoromethy1-biphenfl 2o' carbonyl) -amino] -phenyl)-acetic acid 3, 3-bis- 0 ethylcarbaxnoyl-3-phenyl-propyl ester, {3-isobutyl-4-[I(C -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbamoyl-2-phenyl-ethy- ester, 2-(2-{3-isobutyl-4-1 (4'-trifluoromethyl-biPhelYl-2carbonyl) -amino] -phenyl) -acetoxymethyl) -2 -phenyl-malonic diethyl. ester, 2-(2-{3-chloro-4-[(4'-trif1uoromfethY1-biPhel2carbonyl) -amino] -phenyl}-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-(2-{3-bromo-4-[ (4'-trifluoromethy.-bipbelyl-2car-bonyl) -amino] -phenyl)l-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-{3-dimethyJlcarbamoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl) 2-phenyl-malonic acid diethyl ester, {3-dimethylcarbamoyl-4- -trifluoroniethylbiphenyl-2-carbonyl) -amino] -phenylli-acetic acid 2-phenyl- 2, 2-bis-propylcarbarnoyl-ethyl ester, 13-methylcarbamoyl-4-[1(4 '-trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbarnoyl- 2-phenyl-ethyl ester, 3-dimethylcrbamfl-4- '-trifluorometkqlen biphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 3, 3-bisethylcarbamoyl-3 -phenyl-ethyl ester, o 5 2- (2-{3-diethylcarbamOyl-4- '-trifluoromethylbiphenyl-2-carbOrlyl) -amino] -phenylj-acetoxymethyl) -2- 00 ci phenyl-maloflic. acid diethyl ester, o) {3-benzylcarbafoyl-4- -trifluoroinethyl-bipheflyl- 02-carbonyl) -amino] -phenyij)-acetic acid 2, 2-bisethylcarbamoy.- 2 -phenyl-ethyl ester, 3-dirnethylcarbamoyl-4- -trifluorornethyl-bipheny- 2-carbonyl) -amino] -pheriyl)-acetic acid 414' -bisethylcarbanoy-4 -phenyl-butyl ester, {3-diethylcarbafoyl-4- -trifluorornethyl-biphenyl-2 -carbonyl)-anino] -pbhenyll-acetic acid 2, 2-bisethylcarbifoyl- 2-phenyl-ethyl ester,- 3-diisopropylCarbafoyl-4- -trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbanoy-2 -phenyl-ethyl ester, 2-{3-diethylcarbamoyl-4- -trifluorornethylbiphenyl-2-carbOnyl) -amino] -phenyl)-acetoxymethyl) -2pheny1-mrflic acid diethyl ester, 2- (2-{3-diisopropylcarbarnoyl-4-[ -trifluoromethylbiphenyl-2-carbOnyl) -amino] -phenylj'-acetoxyrnethyl) -2phenyl-maloniC acid dietbyl ester, 3-C isopropyl-methylcarbanoyl) -trifluororethyl-biphenyl-2-carbOnyl) -amino] -phenyl)-acetic acid 2,2bis-ethylcarbamnOy1-2-phefl-ethYl ester, 2- (ethy1-methylcarbamoflO) -trifluo-romethyl-biph'enyl-2-carbonyl,)-amino] -pheny l)-acetoxymethyl) 2-phenyl-malonic acid diethyl ester, Mn (ethyl-methylcarbafoyl) (4 '-trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 2, 2-biso 5 ethylcarbamoyl-2-phenyl-ethy. ester, (ethyl -methylca-rbalOyl) (4 '-trifluoromethyl- 00 biphenyl- 2-ca-rbonyl) -amino]I -phenyl) -acetic acid 3 .3-biso) ethylcarbamoyl- 3-phenyl-propyl ester, 0 (piperidine-I-carbonyl) -trifluoroinethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 2, 2-bisethylcarbamoyl-2-phenyl-ethyl ester, 3- (pyrrolidine-1-carbol))-4- -trifluoromethylbiphenyl-2-carbony-) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, (methyl-propylcarbamoyl) -trifluoroinethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, {3-(methyl-propylcarbanoyl) -trifluorcnnethylbiphenyl- 2-carbonyl) -amino] -phenyl) -acetic acid 3 ,3-bisethyl carbamnoyl 3 phenyl -ethyl ester, (dimethylcarbamoyl) triluoromethyl biphenyl-2-carbonyl) -amino] -phenyl)l--acetic acid 2-ethylcarbamoyl-2 -phenyl-ethyl ester, 2-phenyl-2- (2-{3-(pyrrolidine-1-carbolyl) tritluoromethyl-biphenyl-2-carbolyl) -amino] -phenyl)acetoxymethyl)-malonic acid diethyl ester, 2-phenyl-2- (piperidine-i-carbonyl) trifluorornethyl-biphenyl-2-carbonYl) -amino] -phenyllacetoxymethyl)-malonic acid diethyl ester, 3-dimethylcarbafoyl-4- -trifluoromethylbiphenyl- 2 -carbonyl) -amino]I -phenyl) -acetic acid 2-phenyl-2propionylamino-ethyl ester, (3-dimethylcarbamOyl-4- '-trifluoromethylbiphenyl- 2- carbolyl) -amino]I -phenyll -acetic acid 2-phenyl-2propionylamino-ethyl ester, 00 ci {J3-dirnethylcarbamoyl-4- -trifluoromethylobipheny1-2-CarbOlyl)-aliflO>Phefll-8CetiC acid 2-(2,5ci -dioxo-pyrrolidil-1-yl) -2-phenyl-ethyl ester, 3-dimethylcarbalnOyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyll-acetic acid 2ethylcarbanoyl-beflZyl ester, 3-dirnethylcarbarnOyl- -trifluoromethylbipheny-2-car~Oflyl}-amil]-phenyl)-acetic acid 2ethylcarbamoylmethyl-belZYl ester, 3-direthylcarbamoyl- 4- *-trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2isopropylamino- 2-phenyl-ethyl ester hydrochloride, 2- (2-{3-di-methylcarbafOyl-4- -trifluoromethylbiphenyl-2-carbonYl) -amino] -phenyl)-acetoxy) -ethyl] -2phenyl-malonic acid diethyl ester, 2-(2-{I3-dimnethyJlcarba1UOYl-4-[ (4'-fluoro-biphenyl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl- inalonic acid diethyl ester, 2-(2-{4-[.(4'-bromo-biphefl-2-carboflyl)-amiflo]3djmethylcarbanoyl-pheflyll-aCetOXyethyl) -2-phenyl-malonic acid diethyl ester, {3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amuino] -phenyl)-acetic acid 2acetylamino-2-phenyI-ethYl ester, (3-dimethylcarbamOy.- 4 -triflu'orcomethy1enbiphenyl-2-carbOlYl) -amino] -phenyll-acetic acid 2butyrylamino- 2-phenyl-ethyl ester, o 5 2- (2-(3-dimethylcarbalOyl- 4 -trifluoromethylbiphenyl-2-Carbolyl) -amino] -pheny11-aCtOXYmfethYl) -2- 00 phenyl-maloflic acid disnethyl ester, o ylpnyl2(-3dimtycrbmy 0 trifluoromethyl-bipheflYl-2-Cari)onYl) -amino] -phenyllacetoxyrnethyl)-malOlic acid diethyl ester, 2-cyclohexy1-2-(2-{3-di~fethY1Carbamoyl- 4 -I trifluoronethyl- -biphenyl carbonyl) -amino] pheny1}-acetoxymethy)-la1Olic acid diethyl ester, (4'-chloro-biphefyly2-Carbofl)-aminoP>3 dimethylcarbamhOy1-Phefl>aCtOXYmrethYl) -2-phenyl-malolic acid diethyl ester, 2-2f-('aey-ihny--abnl-mnl3 dimethylcarbamoyl-phe2Yl) -acetoxymethyl) -2 -phenyl-mfloflic acid diethyl ester, 2-2(-('caobpey--abnl-mn]3 dirnethylcarbanoyl-phelyl} -acetoxymethyl) -2-pheny-ma~1OliC acid diethyl ester.

2-(2-{3-dimethyCarbamoflY>44(4L-methyl-4' trifluoromethyl-biphelYl-2-CarbOlYl) -amino] -phenyl)acetoxyniethyl)- 2-phenyl-naloflic acid diethyl ester, 2- (2-{3-disnethylcarbafOYl- 4 [(5-methyl-4' trifluorornethyl -biphenyl carbonyl) -amino] -phenyl)Iacetoxymethy)-2-PhelYl-falOnic acid diethyl ester, {3-climethylcarbafloYl- 4 -trifluoromfethylbiphenyl-2-Carbolyl) -amino) -phenyl)-acetic acid 2methanesulfonylaminfO-2-phanfly-thYl ester, MC 3- (2-{3-dimethylcarbafOyl-4-[ -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetoxy) -2-phenylpropionic acid ethyl1 ester, {3-dirnethylcarbafoyl-4- -trifluoromethyl- 00 biphenyl-2-carbolYl) -amino] -phenyl) -acetic acid 2- (methylo propionyl-amino)-2-phenyl-tthYl ester, o 2-[3-(2-t3-di-methylcarbamloyl-4-[(4-trifluoromethYlbiphenyl-2-carbOlyl) -amino] -phenyl)-acetoxy) -propyl] -2phenyl-malonic acid diethyl ester, 2-(2-{3-dimethylcarbamlY-4-[(5-methOXY- 4 trifluoromethyl-.biphelyl-2-CarbOflyl) -amino] -phenyl) acetoxymethy]-2-phenyl-malOliC acid diethyl ester, 2-2(-5clr-'t~furmty-ihnl2 carbonyl) -amino] -3-dimethylcarbamoyl-phelYll acetok'yinethyl)-2-phel-maloflic acid diethyl ester, 2-(2-(3-dimethylcrbamfoyl-4-[(6-methyl-4trifluoromethyl-biphelyl-2-carbolYl) -amino] -phenyl) acetoxymethyl)- 2-phenyl-maloflic acid diethyl ester, 2- (2-{3-disnethylcarbamOyl-4-[ C4' -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxymethyl) -2phenyl-malonic acid di-2 2-trifluoroethyl ester, 2-(2-{3-dimethylcarbamoyl-4-[(2'-fJluorO-4'trifluoromethyl-bipheflYl-2-carbolYl) -amino] -phenylJacetoxymethylj-2-phenyl-fllofliC acid diethyl ester, 2- (2-(5-dimethylcarbalnoyl-2-fiUOrO-4- trifluorometbyl-biPheflyl-2-carbonyl) -amino] -phenyl) acetoxcymethyl)-2-phelyl-falOflic acid diethyl ester, trif luoromethyl-biPhefll2-CarbOl) -amino] -phenyllenacetoxymethyl)-2-pheflYl-maOfliC acid diethyl ester, 2- 2-{3chloro-5-dimethY1CarbamOYl- 4 o 5 triiluoromethy1-biPhefl2-CarbonYl) -amino] -phenyllacetoxymethyl)-2-phelYl-malOfliC acid diethyl ester, 00 '42-(2-{3-dimthy1carbmoy1-4-(3'fluoro'- 0 trifluoromethyl-biphefll2-CarbOlYl)-amino] -phenyllo acetoxymethyl)-2-PheIYl-falOliC acid diethyl ester, 2-2(-3-hoo4'tilooehl biphenyl- 2-carbonyl) -amino]I -3 -dirnethylcarbamOY3l-Phefl)Iacetosymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-{3-dimethylcarbamtOY1- 4 -trifJluoromethylbiphenyl-2-carbOflyl) -amino] -phenylj'-aCetOXYmfethYl) -2- (5-nitro-pyridfl-2-Y)-raloflic acid diethyl ester, 2- (5-amino-pyridin-2-Y1) -2-(2-f3-dimethyCarbaToy1-4- -trifluoromethY1-biPhefl-2-CarbOnYl) -aminol -phenyl)acetoxymethyl)-maloflic acid diethyl ester, 2- (2-{3-dimethy1Carbamfl-4- -trifluoromethylbiLphenyl-2-carbonyl) -amino] -phenyl)-acetoxYmethYl) -2pyridin-2-yl-malOlic acid diethyl ester, 2-2(-hoo5dmtylabmy--loo4 trifluoromethyl-biphenYl 2 -carbonyl) -amino] -phenyl) acetoxymethyl)-2-phenYl-malolic acid diethyl- ester, 2-2(-rm--iehlcraol2fur--(4'trifluoromethyl-biPhefll2-CarbOlYl)-amino] -phenyl)acetoxynethyl)-2-phelYl-lalofliC acid diethyl ester, 2- (2-(3-dimethylcarbafoyl-4- 1(4' -trifluoromethybiphenyl -2 -carbonyl) -amino] phenyl)l-acetOXYmfethyl) -2 -o tolyl-malonic acid diethyl. ester, 2- (2-(3-dimethylcarbamfOyl-4-[ -trifluoromethylen biphenyl-2-carbonyl) -amino] -phenyl}-acetoxynethYl) -2-rntolyl-malonic acid diethyl ester, o 5 2- (2-(3-dimethy.CarbamOyl-4K (4'F-trifluorome thybiphenyl-2-carbolyl) -amino] -phenyl)-acetoxynethYl) -2 -p- 00 tolyl-malonic. acid diethyl ester, 0 -trifluoromethy-bphel-2-CarbolYl) -amino] -phenyl)acetoxymethyl)-malOliC acid diethyl ester, 2- (3-chloro-pheny1) (2-(3-dimethy1carbwnoyl- 4 -trifluorornethyl-biphelyl-2-Carb~flI) -amino] -phenyl)acetoxyrnethyl)-malOflic acid dietbyl ester, 2-(4-chloro-pheny1)-2-(2-3-diYfethy1carbamoyl- 4 -trifluorornethy1-biPhel-2-CarbolYl) -amino] -phenyllacetoxyrnethyl)-malonic acid diethyl ester, 2- (2-{3-diinethyl-carbamOyl-4- -trifluoroinethylbiphenyl-2-carbonyl) -amino] -phenyll-acetoxymethyl) -2phenyl-succilic acid diethyl ester, 2- (2-{3-dimethylcarbamoYl-4-[ -trifluoromethy.biphenyl-2-carbolyl) -amino] -phenyl}-acetoxymethyl) -2- (2-methoxy-phenyl)-falOfliC acid diethyl ester, 2- (2-{3-diinethylcarbamfoyl-4- '-trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyll-acetoxynethyl) -2- (3-methoxy-phe'yl)-malOflic acid diethyl ester, 2- (2-{3-dimethylcarbaloyl-4- -trifluorornethylbiphenyl-2-carbolyl) -amino] -phenyi}-acetoxymethyl) (4rethoxy-phenyl)-malOflic acid diethyl ester, 2-2(-54-i-rfurmty-lhnl2 carbonyl) amino] dimethylcarbamfl-PhelYl) acetox-ymethyl)-2-pheflyl)-malolic acid diethyl ester-, en 2-(2-(4-(6-ChlOrO-4' -trifluoromethy1-biphelI 2 carboriyl) -amino] -3 -dimethylcarbaROY1-PhelYl) o ~5 acetoxymethyl)-2-phel-alOliC acid diethyl-eSter1 0'2-(2-{3-dimethylcrbamoy1-4-(6-fluoro- 4 00 trifluoromethy-biPhel-2-C8ab'OfYl) -amino] -phenyl} o acetoxymethy1)-2-PhelYl-malOliC acid diethyl ester, o2-L2-(2-(3dimethy1carbaOY4[(5-methYl- 4 trifluoromethyl-biphefll2-CrbOlYl)-amino] -phenyllacetoxymethy1)-2-PhelmalOfiC acid diethyl ester, 2- (2-(3-dimethylcarbafOYl-4- [(5-ethoxy-4 trifluoromethyl-biphenfl2 -carbonyl) -amino] -phenyll acetosyzethyl)-2-PhelYl-malOfliC acid diethyl ester.

2-2(-iehlabmyl4[5iorpx-' trifluoromethy-bPheiY)-2-CarbOl)-amino] -phenyilacetoxymethyl)-2-PhelYl-malOflic acid diethyl ester.

2-1,2- -bis-4' -trifluoromnethy1-biPhenfl 2-carbonyl) -amino] -3 -dimethylcarbanOyl-PhelYl) -acetoxy) ethyl]-2-phelyl-maloflic acid diethyl ester, 2-(2-(3-dimethylcarbBahoy1-4-[(6-methoxy- 4 trifluoromethyl-biPheflyl-2-CarbOnYl) -amino] -phenyl)acetoxymethyl)-2-phenyl-lalonic acid diethyl- ester, 2-(2-{3-dimethylcarbalY- 4 J (3-methyl-4'trifluoromethy1-biPhnY-2-carbonYl) -amino] -phenyl'acetoxymethyl) -2-phenyl-malolic acid diethyl ester, 2-2[-24bstilormty ezyaio-3dimethylcarbaznoyl-phenyll -acetoxyrnethyl) -2-phenyl-malonic acid diethyl ester, dimethy1carb8XflY 4 -xethyl-biphenlJ-2 carbonyl) amino I -phenyl) "aCet OXYmfethYJ.) 2-phenyl--laOfliC acid diethyl ester, 22- [3-dimnethylcarbamlY-4-( 2 -ethYl- 4 o trifluoromethYl-belzOYlamilo) -phenyl] -acetoxymlethyll -2phenyl-maloflic acid diethyl ester, 00 ci ~2-i2-{3-dimethycarbamfl- 4 -ethy1-biphel-2o ~carbony-) -amino] -pheny1}-aCetOXYflethYl) -2-phenyl-maJ-oniC ci acid diethyl ester, 2- (2-{3-dinethylcarbamoflO~-4-[(4' -isopropenylbiphenyl-2-CarbOlyl) -amino] -pheny1)-aCtoxyflthYl) -2phenyl-malolic acid diethyl e-ster, 2- (2-{3-dimethylcarbamfoYl- 4 -isopropylbiphenyl-2-carbOlYl) -amino] -phenyl)-aCetOXYTmethYl) -2phenyl-malOflic acid diethyl ester, [3-dimethylcarbafOYl- 4 -trifluoromethylbiphenyl-2-CabOlYloxy) -phenyl]-acetoxyrethyl) -2-phenylmalonic acid diethyl ester, {3-direthylCarbamoyl- 4 -trifluoroinethylbiphenyl-2 -carbolyl) -amino] -phenyl)l-acetic acid 2-ethyl-2phenyl-butyl ester, (3-dimethylcarbafOyl- 4 -trifluoromethylbiphenyl-2-carborlYl) -amino] -phenyll-acetic acid 1-phenylcyciopropylmethyl ester, {3-dimethylCarba1Doyi- 4 -trifluoroniethylbiphenyi-2-CarbolYl) -amino] -phenyi)-acetic acid 2,2diphenyl-ethyl ester, f3-dirnethylcarbaloyi- 4 -trifluoroniethylbiphenyi-2-CarboflYl)-amino] -phenyl)-acetic acid 1-phenylo cyclopentylinethyl ester, {3-dimethy3caba Oyl- 4 -trifluorometlbiphenyl-2-CarbOrlYl) -amino] -pheny1l)-acetic acid 3-hydroxy- 2 -hydroxymethyl- 2-phenyl-propyl ester, o {3-dimethylcarbaflOYl-4- -tritluoronethyl1- 00 biphenyl-2-CarbOlYl) -amino] -phenyl)l-acetic acid 3-acetoxyci 2-acetoxymethy1-2-pheflYl-PrOPYl ester, o 2-(2-(3-dimethy1Ca-rbamoY14 -trifluoromethyl- Ci biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetOXYmfethYl) -2thiophen-2-Y-lalOfliC acid diethyl ester, 2-{3-dimethylcarbamOY1-4- '-trifluoromfethylbiphenyl- 2-carbonyl) -amino II-phenyl) -acetox-ymethyl) -2 thiophen-3-yl-malOlic acid diethyl ester, 2- (2-(4-dimethylcarbafoYl-5- -trifluoromethylbiphenyi-2-carbOlYl) -amiLno] -pyridin-2-y1}-aCetOXYmfethYl) 2-phenyl-malolic acid diethyl ester, 2- (2-(3-dinlethylcarbamfOYl-44 -trifluoromethylbiphenyl-2-CarbOl) -amino] -pheny1)-acetOXymfethYl) (3methy-thiophefl-2-ylPfalOflic acid diethyl ester,.

2- (2-{3-dimethylcarbafoYl-4- -trifluoronetliylbiphenyl-2-CarbolYl) -amino] -pheny1)-acetOX-Y1TIthYl) -2 rnethyl-thiOphefl-2-Yl) -malonic acid diethyl ester, 2- (2-{3-dimethylCarbrfoYl- 4 -trifluoromethylbiphenyl-2-CarbolYl) -amino] -pheny1)-aCtOXyflflthYl) -2thiazol-2-y-falofliC acid diethyl ester, 2- (2-{3-ethoxy-4- -trifluoromethy1-biPhelYl- 2 carbonyl) -amino] -pheny1> acetoxymfethYl) -2-phenyl-malolic acid diethyl ester, {3-hydroxy-4- -trifluoromethY1-biPhelYl- 2 C-)carbonyl.)-amifl]-phenyl)'-aCetiC acid 2, 2-bisethylcarbafl]- 2-pheflyl-ethyl ester, m {3-methOxy-4-1t(4' -trifluoromethyl-biPheflJ2 carbonyl) -aminolI-phenyJ-)-aCetiC acid 2,2-hiset hylcarbam~Oyl- 2-pheny-ethyI ester, 00 2- (2-{3-methOxy-4- 'trifluoromethY-biPhnflY carbonyl) -amino] -pheny1}-aCtoxyITethYl) -2-phenyl-malolic o acid diethyl ester, 0 {(3-xnethosy-4-.[ -trifluoromethY1-biLPhefll 2 carbonyl) -amino]I-phenyl)-acetic acid 2-phenyl-2 ,2-bispropylcarbamnoyb-ethYl ester, (3-znethoxy-4- -trifluoromethyl-b~hel- 2 carbonyl) -amino] -phenyJl}-aCetic acid 3, 3-bis-ethylcarbamflY13-PheflYl-ProPYl ester, {3-ethoxy-4- -trifluoromethy1-biPhefyl-l> carbonyl) -amino] -phenyll-acetic acid 2,2-hisethylcarbamOY>2-PheflethYl ester, (3-ethoxy-4- -trifl1Aoromfethyl-biphel> 2 carbonyl) -amino] -phenyll-acetic acid 3, 3-bisethylcarbamfoyl -3 -phenyl -propyl ester, 2- (2-{3-iSOprOpOXY-4-[(4' -trifluoromethyl-biPhelYl- 2-carbonyl) -amino] -phenyl}-acetOXYfllthYl) -2-phenyl-nalolic acid diethyl ester, {3-isopropOxy-4- -trifluoro'methyl-biPhelyl'2carbonyl) -amino] -phenyl1-acetic acid 2, 2-hisethylcarbafll-2- phenyl -ethyl ester, {3-isopropOxy-4- -trifluoromfethYJ.-biPheflYl-2carbonyl)-amifl]-phenyl)-acetic acid 3,3-bisethylcarbamOYl-3-PhelYl-Propyl ester, o{ 3-proPOxW-4-[(4' -trifluoromethy1-biphenYl- 2 carbonyl) -amino) -phenyl)-acetic acid 2, 2-bisethylcarbaylJ- 2-phenyl-ethyl es§ter, {3-benzyloxy-4- 1(4' -trifluoromethY1-biphel-l 2 o 5 carbonyl) -anino]-pheiiyl}-aCetiC acid 2, 2-bisethylcarbamfl-12-phenfl-thYl ester, 00 ci 2- (2-.(,3-benzyloxy-4- -trifluoromethy-biphelyl- 2 o ~carbonyl) -amino] -phenyl}-acetOxyfethYl) -2-phenyl-mfalOflC ci acid diethyl ester, 2-,(2-{3-hydroxy-4- -trifluoromethyl-biPhenYl- 2 carbonyl) -amino) -phenyl)-acetOxYflethYl) -2-pheny1-ma1Oflic acid diethyl ester,' 2-(2-[3-methoxy-4- -trifluoromethyl-biPhefl> 2 carbonyloCy) -phenyl] -acetoxymnethyJ.-2-Phefllmalonic acid diethyl- ester, 3-dimethylamiflO- 4 -trifluoromethY1-biphel-l 2 carbonyl) -amino) -phenyl)-acetic acid. 2, 2-bisethylcarbam~oyl -2 -phenyl -ethyl ester, {3-piperidfl-1-Yl- 4 -trifluoromethYl-biPhelYl- 2 carbonyl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbafOyl- 2-phenyl-ethyl ester, {3-pyrrolidifl-1-Yl- 4 -trifluoromethY1-biphelYl- 2-carboYnyI)-amilo]-phefl1acetic acid 2,2-bisethylcarbamfoyl- 2-phenyl-ethyl ester, 2-pheny1-2-(2-{3-Piperidifl-1-yl-4-'[( 4 trifluoromethyl- biphenyl-2-carboflyl) -amino) -phelylacetoxymethyl)-malolic acid diethyl ester, 2-pheny1-2-.2{3-pyrrolidin-1yl 4

I(

4 trifluoromethy1-biphefyl12-carbonYl) -amino] -phenyllacetoxymethyl)-malOfliC acid diethyl ester, 2- (2-(3-dimethylafiflO-4- -trifluoroinethylen biphenyl-2-CarbOlYl) -amino] -phenyl)-acetOX~fethYl) -2phenyl-malOflic acid diethyl ester, o 5 (2-(3-morphoinf-4-y1- 4 (4'-triflUOrOImethYlbiphenyl- 2-carbonyl) -amino] -phenyl}-acetOXYmfethYl) -2- 00 ci phenyl-malolic acid diethyl ester, o ~2-(2-{3-diethylafiflo-4-d -trifluoronlethYl- 0 ~biphenyl-2-Car~Oflyl) -amino] -phenyll-acetOxynethYl) -2phenyl-malonlic acid'diethy. ester, carbonyl) -amino] -phenyl)-acetoxy) -ethyl) -2-phenyl-malonic acid diethyl ester, 2-phenyl-2- -trifluoromethy1-biPhefl-2carbonyl) -amino] -phenyl}I-aCetoxymethYl) -maloni-c acid diethyl ester, 2-hnl2[-2{-('trfurmty-ihnl2 carbonyl) -amino] -phenyl}-acetOXy) -ethyl] -malonic acid diethyl ester, (3-1 -trifluoromethyl-biphefl2-CarbonYl) -amino]phenyl)-aCetiC acid 3, 3-bis-ethylcarbIfOYl-3-PhelYlpropyl ester, -trifluoromethyl-biphenfl-2-CarbonYl) -amino) phenyl)-acetic acid 2, 2-bis-ethylcarbalY-Phefl-ethYl ester, -trifluoromnethyl-biphel-l2-carbonYl) -amino]phenyll-acetic acid 3-phenyl-3, 3-bis- propylcarbanoylpropyl ester, 2'1-21-ehl314-rilooehlbpeycarbonyl) -amino) -phenyl}-acetoxy-ethYl) -2-phenyl-m~aloflic acid diethyl ester, carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-maloliC acid diethyl ester, -trifluoromethyl-bipheflYl-2-CarbOnYl) -amino] phenyl)-aceti-c acid 3, 3-bis-isopropylCarbamoflO -3phenyl-propyl ester, {2-methyl-3- -trifluoromethyl-biphelYl- 2 carbonyl)-arninO]-phefl)l-aCetiC acid 3. 3-bisethylcarbamOyl-3-pheflPrOPYl ester.

(2-methyl-3- -trifluoromethyl-biphelYl- 2 carbonyl) -amino] -phenyl)-acetic acid 4, 4-bisethylcarbamoyl-4-pheflYl-butYl ester, (2-metbyl-3- -trifluoromethyl-biphelYl- 2 carbonyl) -amino] -phenyll-acetic acid 3-phenyl-3, 3-bispropylcarbamoyJl-propyl ester, {2-methoxy-3- -trifluoromethyl-biPhelYl-2carbonyl) -amino] -phenyl)-acetic acid 3, 3-bisethylcarbamoyl-3-phel-PrOPYl ester, 2-[2-(2-{2-methoxy-3-[ (4'-trifluoromnethy1-bipheflyl- 2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenylmalonic acid diethyl ester, {2-ethoxy-3-[F(4' -trifluoromethyl-biPhefll2carbonyl) -amino]-phenyl)-acetic acid 3, 3-bisethylcarbafoYl-3-PheflYl-PrOPYl ester, 2- (2-{2-ethoxy-3- -trifluoromethyl-biPhel-2carbonyl) -amino] -phenyl) -acetoxy) -ethyl] -2-phenyl-tnalonic acid diethyl ester, 5biphenyl-2-CarbOlYl) -amino] -phenyll-aCetoSY) -ethyl] -2en phenyl-malonic acid diethyl ester, 2-[2-(2-{2-mtoxethOXtahbylYI 3 4(4' -trifluorofethYlo biphenyl-2-CarbonflY))-amino] -phenyl)-acetOsY) -ethyl] -2phenyl-naloflic acid diethyl. ester, 4-('til~oehbiphenyl-2-Cabf~)-mn]-hnl- COY) etyl -2benzoic acid 2- 2, 2-trifluorO-ethylCatbaIOYl) -9hfluoren-9-yl]-BthYl ester, -trifluoromethyJl-biphenflY2-CarbonYl)-am±no] benzoic acid 2-[9h-fluoref-9-yl]-ethYl. ester, n-biphenyl-2-yl-terephthalamic acid (2,2,2trifluoro-ethylarbamfOyl) -9h-fluoren-9-YI] -ethyl ester, 4- -trifluoromethy1-biPhefyl-l-carbonYl) -amino] benzoic acid 2- [(biphenyl-2-CarbOflYl) -amino] -ethyl ester, -trifluoromethyl-biPheflYl-2-carbOnYl) -amino]benzoic acid 2- 2biphenyl-2-Yl-acetYlamilo) -ethyl ester, 4- [(4'-til ormty-ihny -abnl-amino) benzoic acid 3-naphthalefl-l-yl-3-(2.2,2-trtfluoroethylcarbafoyl) -propyl ester, -trjfluorornethyl-bipheflyl-2-Carboflyl) -amino] benzoic acid 3-12- 2-trifluoro-ethylcZarbalOYl) naphthalen-a-y1] -propyl ester, 4- -trifluoromethyl-bipheflJ-2CarbonYl) -amino] benzoic acid 3, 3-diphenyl-3- 2,2-trifluoroethylcarbanoyl) -propyl ester, 4 ''trifluoromethYl-biPheyll2-cabonY1)-rrlino] benzoic acid 3-ihf-2-Y 1 yl 3 2-trifluoroen ethylcarbalfOyl)-PrOPYl ester, 00 -trifluorOmfethYl-biPhefl2-carbonYl) -amino] o 5 benzoic acid 3 2penl8-(2.2,2-trifluoroethylcarbalfOyl)-nPOP ln1--ehl ester, -trif luoromethYl-biPhefl-2cabonY1) -amino] 0benzoic acid 312,-[8-(2,2,2-triflrO 0 22,-flooethylcarbalflyl)-nptae-1Y]-ethoyl ester -trifluoromethyl-biPhefl2-carbonyl) -amino] benzoic acd3-2cidrophny)3-(2,6,-i1oro 2 2thlrifol rOpetYl estr,~~)-rpletr 421(4 etrluor(2-fl154t r~i~flol-2h-Cbnhel)-ncabnlmnlbenzoylx)ehl-aoic acid dity ehlabmy.-rPlester, 22e--(2y- 4 -4 (4'-trifluorOmfethY1-biPheflYl- 2 -amino] -benzoyloxy)-ethYl) -maheymonic acidy delester, 2- (2-(3-rnehl-4-[ -trifluoromfethY1-biPhel-l 2 arbonyl) -amino] -benzoyloxyl-ethYl) -2-phenyl-mlalOflic acid diethyl ester, 2-phenyl-2-{2-1 4 4 (4'-trifluorOmlethYl-bipheyl-l 2 carbonyloxy) -benzoy-oxy]-ethyl)-malofliC acid diethyl ester, 4- -trifluoromethyl-biPheyl-l2-carbonYI) -amino] benzoic acid 3, 3-bis-ethylcarbamflY13-PhefllProPYl ester.

4' -trifluoromethyl-biphel>2-carboxcylic acid 4- (3,3bis-ethylcarbamfOyl-3-phel1PrOPOxcycarbonY) -2-chiorophenyl ester, 4. -trifluoromethy1-biPhefl-b2-Carbo2Wlic acid 4- (3,3bis -ethylcarbanOyl- 3-phenyl-propoxycarboflYl) -phenyl1 ester, o 4' -trifluoromethy1-biPhefl-2-crbox2Ylic acid 4- (3,3bis-ethylcarbamOyl-3-PheflI-PrOPOXYCarbonYl) 6-dichioro- 00 phenyl ester.

o 2- (2-(3-ethoxycarbOflyl-4- -trifluoromethyl- Ci biphenyl-2-CarbOflyl) -amino) -phenyl-acetox-YmfethYl) -2phenyl-malolic acid diethyl ester, 2- (3-{3-dimethylCarbamoyl-4-[ (4 '-trifluoromethylbiphenyl-2-CarbOlYl) -amino] -pheny11-proPlYOXYmfethYl) -2phenyl-malolic acid diethyl ester, -trifluoromethyl-biPhefylY-CarbonYl) amino] -phenyll-prOpiOflic acid ethylcarbamOyl-Phelmethyl ester, (2,2-i-tycramy -hnletoyabnl methyl) -trifluoromethyl-biPheflYl-2-CarbOnYl) amino]-benzoic acid benzyl ester, 5- 2.bis-ethylearbamoyl-2-Phel-lethOSyca-rbonYl' methyl) -trifluoromethYl-biphelYl-2-CarbonYl) amino] -benzoic acid, 2 -bis-ethylcarbamOYl-2-PheflYl-etho2CycarbonYlmethyl) -trifluoromethy1-biPheflYl-2-CarbonYl) anino]-benzoiC acid ethyl ester, 2 -bis-ethylcarbamoyl-2-PhelYl-ethO)CycarbOll methyl) -trifluOromethy1-biphel2-CarbonYl) amniro-benzoic acid methyl ester, 2- (2-{3-benzylOxycarbOflyl- 4 -trifluoromethylbiphenyl-2-carbol) -amino] -phenyl)-acetoxyulethYl)- 2 phenyl-malonic acid diethyl ester, carbonyl) -amino] -pheny. }-acetoxymethy)- 2-phenyl-malonic acid diethyl ester, 2- (2-(3-isopropoxycarbolyl-4- -trifluorometbyl- 00 biphenyl-2-carbOnyl) -amino] -phenyl}-acetOxymethYl) -2o phenyl-malonic acid diethyl ester, 0 2- (2-(3-methoxycarbOnYl-4-[ -trifluoromethylbiphenyl-2-carbOnyl) -amino] -phenyl}-ace toxymethYl) -2phenyl-malonic acid diethyl ester, 2- (2-{3-acetylamino-4- -triftuoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl)-acetoxylethYl) -2-phenyl-inalonic acid diethyl ester, 2- (2-{3-methoxycarbonylamikO-4- -trifluoroinethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxyxethYl) -2phenyl-malonic acid diethyl e ster, 2-(2-{3-(4-methyl-thiazol-2-Y)- 4

-I(

4 t trifluoroznetbyl-bipheflyl-2-CarbOnyl) -amino] -phenyl)acetoxyrnethyl)-2-phelyl-malo:lo acid diethyl ester, 2-hnl2(-6[4-rfurmty-ihnl2 carbonyl) -amino] -biphenyl-3-yl-acetoxymfethY-) -malonic acid diethyl ester, 2-2(-oml4[4-rfurmty-ihnl2 carbonyl) -amino] -phenyll-acetoxyethyl) -2-phienyl-malonic acid diethyl ester, 2-{3-dimethylaminofethyl-4- -trifluoromethylbiphenyl-2-carbOflYl) -amino] -pheny11-3-acetoxymlthYl) -2phenyl-maJ-onic acid diethyl ester, (2-(3-methoxy-methy1CarbamOYl) trifluoromethyl-biPhenYl2-carbonYl) -amino] -phenyl} -3acetoxymethyl) -2 -phenyl-malOflic acid diethyl ester, 2- (2-{3-isobutyryl-4- -trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl}-3-aCetOXYmflthYl) phenylinalonic acid diethyl ester, and 2-(2-{3-(1-hydroxy-2-flethYl-PrOPYl)- 4 4 trifluoromethyl-biPhefl-l2-CarbOnYl) -amino] -phenyl)acetoxymethyl)-2-PhenYl-malOfliC acid diethyl ester; (24) The ester compound or a prodnig thereof, or a phiarmaceutically acceptable salt of either according to the above which is selected from the group consisting of -trifluoromethy1-biPhenYl-2-carbOnYl) -amino] phenyl)-acetic acid 2, 2-bis-ethylcarbamfoYl) -2-phenylethyl ester, 2-phenyl-2-{2-[4-L -trifluoromethYl-biphenyl>2 carbonyloxy) -phenyl] -acetoxymethyll-malonic acid diethyl ester, 2-(2-{3-Inethyl-4-[ -trifluoromethyl-biphelYl-2carbonyl) -amino) -pheny1)-acetoxyImethYl) -2-phenyl-malonic acid diethyl ester, 2- Emethyl- -trifluoromethyl-biphenYl'2carbonyl) -amino] -phenyl}-actoxyfllthYl) -2-phenyl-nialonic acid diethyl ester, {3-ethyl-4- -trifluoromethYl-biphenYl>2 carbonyl)-amino-2-phenYll-acetic acid 2,2-bisethylcarban1Oyl-phenyl ethyl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) -amino]I -phenyl}--acetOXYmfethYl) -ialonic acid diethyl ester, carbonyl) -amino) -phenyl--acetOX-YmfethYJ.): inalonic acid ajisopropyl ester, -trifluoromethyl-biPhefylY1-carbOnYl) -amino] 00 ciphenyll-acetic acid 2-phenyl-2,2-bis-(2,2,2o ~trifluoro-ethy.CarbafOYl) -ethyl ester, carbonyl) -amiLno] -phenyl}-acetOxymethyl) -malonic acid dimethyl. ester, 2-cyclopentyl-2-( -trifluotomethylbiphenyl-2-carbOlyl) -amino] -phenyl}-aCetOXymethYl) -Ialonic acid diethyl. ester, 2-phenyl-2-(2-{4-L -trifluoromethyl-biPhelyl-2carbonyl) -amino] -phenyl}-acetOxyfethYl) -mnalonic acid dicyclohexyl ester, -trifluoromethYl-biphelyl-2-carbOnYl) -amino] phenyll-acetic acid 2 ,2-bis-cyclohexylcarbIfoyl-2phenyl ethyl ester, [(4'-.trifluoromethy1-biPhelYl-2-c~tbOlYl) -amino] phenyl)-aceti-c acid 2 -phenyl-2, ,2-bis -pheflylcarbamol -ethyl ester, -trifluoromethyl-biPhelyl-2-carbolYl) -amino] phenyll-acetiC acid 2, 2-bis-isopropylcabamfOYl-2-PhelYlethyl ester, 2-benzyl-2- '-trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyll-acetoxymethYl) -malonic acid diethyl ester, carbonyl) -amino] -pheny1)-aCetOXYme1thYl) -2-phenyl-maOliC Mn acid diethy. ester, 4' -trifluOrOmfethY1-biPheylY12-carboxcylic acid 4- [2pheny1-2,2-biS(2,2,2trifuoro-ethycarbaIoyl)ethoxycarbOly-llethYl] -phenyl ester, 00 biphenyl-2-carboxylic acid 4-[2-phenyl-2,2-biso 2-trifluoro-ethYlCarbamOYl) -ethoxycarbOlIethYl- 0 phenyl. ester, 2-cyclohexyl-2- 1(4' -trifluoromethY1-biPhelYl- 2-carbonyl) -amino] -pheny1)-acetOX-YmfethYl) -malonic acid diethyl ester, (biphenyl-2-CarbOflYl)-Wfifo]PhenYl-acetic acid 2-phenyl-2, 2-bis- (2,2,2-trifluOrO-ethY1CarbamOY-) -ethyl ester, 2-phenyl-2- (2-(2-trifluOrOmethYl-4 trifluoromethY1-biPhenfl-2-carbonYl) -amino] -phenyJacetoxymethyl)-lalolic acid diethyl ester, -trifluoromethYJl-biPhenfl2-carbonYl) -amino] phenyll-acetiC acid 2. 2-bis-methy1carbamlY-2-Phelethyl aster, 2-pyridif-2-yl2-12-( 4 -trifluoroinethylbiphenyl-2-CarbOl) -amino] -pheny1)-aCetOXYflethYl) -ralonic acid diethyl ester, 2-pyridin-3-yl-2-(2-( 4 -[(4'-trifluoromfethYlbiphenyl-2-carbOlyl) -amino] -phenylj'-acetOXYmethY.) -malonic acid diethyl ester, 4' -trifluoroznethyl-biphel-l2-carbxcYlic acid 4- 2-bis-ethylcarbamoyl) -2-pheny-ethOXYcarbolmfthYl) o phenyl. ester, 2-pheny1-2-(2-{3-trifJ-uoromlethy1-4( 4 en trifluoromethy1-biPhenY-2-CarbOfl)-ainO] -phenyll acetoxymethyl)-alOfliC acid diethyl ester, O 5 '-trifluoromethyl-biphelyl-2-CarbolYl) -amino]phenyll-acetic acid 2, 2-bis-butylcarbaxnoyl-2-PheflYl-ethYl 00 ci ester, o 3-methyl-4- -trifluoromethyl-biphelYl-.2ci carbonyl) -amino] -phenyl)-acetic acid 2. 2-biLs-ethylcarbamoyl- 2-phenyl-ethyl ester, 2- -methyl-biphenyl-2-CarbOlYl)-amnino]phenyl) -ace toxynethyl) 2 -phenyl -malonic. acid diethyl ester, (4'-.methoxy-bipheny-2-CarbOl)-alifO] phenyl}-acetox-ym ethyl) -2-phenyl-inalonic acid diethyl ester, -trifluoromethyl-biphelyl-2-CarbOlyl) -amino]phenyl)-acetic acid 3, 3-bis-ethylcarbaxnoy1-3-Phefyli-PrOPY1 ester, '-trifluorornethyl-biphelyl-2-CarbOlyl) -amino] phenyl) -acetic acid 3 -phenyl- 3,3 -bis -propylcarbanioyl -propyl ester, (4-[(bipheny-2-CarbOl)-amifl-phenfl]TaCetiC acid 2 .2-bis-ethylcarbmfly-2'-phefl-ethYl ester, 2-phenyl-2- [(3'-trifluoromethyl-biphenyl -2carbonyl) amino]) -phenyl)}-acet oxymethyl) -malonic acid diethyl ester, 4' -trifluoromethy1-biphenY1-2-carbOXYliC acid 4- 2-bis-ethylcarbamoy1)-2-phefl-ethoxycarbOflYlmethYlh 2-chioro-phenyl ester, 2-(2-{4-[isopropyl.-(4'-trif1uoromethy1-biphefyl>2carbonyl) -amino] -phenylj-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, mn 2- [cyclohexyl- -trifluorornethYl-biPhelYl-2carbonyl) -amino] -phenyl)-acetOxcymfethYl) -2-phenyl-malonic acid diethyl ester, 00 carbonyl) -amino] -phenyl)-acetoxyfethy-) -malonic acid o dipropyl ester, carbonyl) -amino] -phenyl)-acetoxymnethYl) -malonic acid diisobutyl ester, 4 Z. trifluoromethyl-biphenyl-2-OarbOflYl) amino] -phenyll-acetic' acid 2 ,2-bis-isobutylcarbamoyl-2phenyl-ethyl ester, (4-1(4 '-trifluoromethyl-biphefl-2-CarbOlYl) amino]-phenyl)-acetic acid -2,2-bis-(3-methylbutylcarbaioyl) -2-phenyl-ethyl ester, 2- [ethyl- -trifluoromethyl-bipheiyl-2carbonyl) -amino] -phenyll-acetoxymfethyl) -2-phenyl-malonic acid diethyl ester, -chloro-biphenyl-2-Carbolyl) amino] -phenyl}-acetic acid 2 ,2-bis-ethylcarbamOyl-2-phelylethyl ester, -dichloro-biphenyl-2-CarbOlYl) amino] -phenyl}-acetic acid 2, 2-bis-ethylcarbamOYl-2-PhelYlethyl ester, {3-netbyl-4- -trifluoromethyl-biphenyl-2carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2 ,2-bispropylcarbamoyl-ethyl ester, 4- -trif luoromethYl-biPenYl-2caboly'l) -amino]phenyl)-acetic acid 2. 2-bis- 2-rethOXy-ethY1Ca-Lbamfl) -2en phenyl-ethyl ester, 2-(2-{3-ethyl-4-[ (4'-trifluOrOmfethY1-biPhefll 2 carbonyl) -amino] -pheny1}-aCetOXymethY1)2-Pheflmalonic acid diethyl ester, 00 (3-isopropyl-4- -trifluoromnethY1-biPheflYl- 2 ocarbonyl) -amino] -phenyl-acetic acid 2, 2-bis- 0 ethylcarbamoyl-2-PheflYl-ethYl ester, 2-(2-{3-isoprOpyl-4-[ -trifluoromethyl-bipheflYl- 2 carbonyl) -amino] -pheny1}-acetOXYmlethYl) -2-phenyl-malOflic acid diethyl ester, carbonyl) -amino] -phenyll-acetic acid 3, 3-bisethylcarbamOyl-3-phefllPropyl ester, 3-isobutyl-4- -trifJluoromnethY1-biPhefYl-2 carbonyl) -amino) -phenyll-acetic acid 2, 2-bisethylcarbamOyl- 2-phenyl-ethYl ester, 2- (2-{3-isobutyl-4- -trifluoromethy1-biphe-l-2carbonyl) -amino] -pheny1)-acetOXylethYl) -2-phenyl-maloflic acid diethyl ester, 2-(-3clr--('tifurmty-ihnl2 carbonyl) -amino] -phenyl)-acetOXYlDethYl) -2-phenyl-fa-Oflic acid diethyl ester, 2-2(-rm--('tifurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxyfethYl) -2-phenyl-ma-ofliC acid diethyl ester, 2- (2-{3-dimethylcarbamoyl- 4 -trifluoromethylbiphenyl-2-carbolYl) -amino] -phenyl}-acetOxYlfethYl) -2phenyl-malonic acid diethyl ester, (1){3-diiuethylcarbamOyl-4- -trifluoromethylen biphenyl-2-carbonyl) -amino] -phenyl)-acetiC acid 2-phenyl- 2, 2-bis-propylcarb1ly-ethy1 ester, o 5 {3-methylcarbwfloyl-4- '-trifiuoromethY1-biPhenfl- 2-carbonyl) -amino] -phenyll-acetic acid 2,2-his- 00 '4 ethylcarbamoyl- 2-phenyl-ethyl ester, VS C3-dimethylcarbamOyl-4- -trifluoroinethylbiphenyl-2-carbOflyl) -amino] -phenyl)-acetic acid 3.,3-hisethylcarbanoyl- 3-phenyl-propyl ester, 2- (3 -diethylcarbamoyl trtluoromethyl biphenyl-2-barbolyl) -amino] -phenyll-'acetoxyfethYl) -2phenyl-malolic acid diethyl ester, {3-benzylcarbaDOyl-4- -trifluoromethyl-bipheny- 2-carbonyl) -ami-no] -phenyl}-acetio acid 2,2-hisethylcarbanoyl- 2-phenyl-ethyl ester,- 3- dimethylcarbamofl trtluoroxnethyl biphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 4, 4-hisethylcarbamoyl-4 -phenyl-buty- ester, 3-diethylcarbanmoyl-4- -tnifluoroxnethyl-biphenyl- 2-carbonyl)-amino] -phenyl)-acetic acid 2, 2-hisethylcarbamoyl-2!-phenyl-ethYl ester, I 3-diisopropycarbamOYJ--4- -tnifluoromethyl-biphen ylr2-carbolyl) -amino] -phenyl)-acetic acid 2,2-hisethylcarbamoyl-2-pheflYl-ethYl ester, 2- (2-f 3-diethylcarbarfOyl-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl}-acetoxyfethYl) -2phenyl-malonic acid diethyl ester, 2- (2-f 3-diisopropylcarbamOyl-4- -tnifluoromethylbiphenyl-2-carbonyl) -amino] -phenyll}-acetox-YnItbY-) -2phenyl-malonic acid diethy. ester, MC (3 (isopropyl -methylcarbalOYl) 4- -tri-fluoroinethyl -biphenyl-2-carbolyl)-all]-phenyl)-acetic acid 2, 2-biso 5 ethylcarbamoy-2-phel-8thYl ester, 2-(2-{3-(ethy1-me1thy1carbamoy)-4[( 4 00 trif luoromethyl-biphelyl- 2- carbonlyl) amino]) -phenyl- VS acetoxynethyl)-2-phelYfalOfliC acid diethyl ester, (ethyl -methylarbafloYl) (41 -trifi.uoromethylbiphenyl-2-carbony-) -amino] -phenyl)-acetiC acid 2, 2-bisethylcarbarnoyl-2-phePYl-ethYl ester, (ethyl -methylcarbaloYl) -trif luoroniethylbiphenyl-2-carbolYl) -amino] -phenyl)-acetic acid 3, 3-bisethylcarbamoyl-3-pheflPrOPYl ester, (piperidin-1-CarbOl)-4- -trifluoroinethylbiphenyl-2-carbolYl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamOyl-2-PheflYl-BthYl ester, (pyrrolidin-1-carbOlYl)- 4 -trifluoromethylbiphenyl-2-Carbolyl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamOYl-2 -pheflyl-ethyl ester, (methyl-propyilcarbamoyl) -trifluorornethylbiphenyl-2-carbonyl) -amino]-phenyl}-aCetiC acid 2 ,2-bisethylcarbamoyl-2-pheflyl-ethYl ester, (methyl-propylcarbafoYl) -4-11(4' -trifjluorornethylbiphenyl-2-carbOlyl) -ami-no] -phenyl)-acetic acid 3, 3-bisethylcarbatoyl- 3-phenyl-propyl ester, ii3-dimethylcartaloyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 2-ethylcarbanoyl-2-pheflyl-ethYl ester, (N 2-phenyl-2-(2-{3-pyrrolidin-1-CarboflYl)- 4 4 trifluoromethyl-biphenyl-2 -carbonyl) -amino) -phenyl) M ~acetoxymethyl)-malonic acid diethyl ester, 2-phenyl-2-(2-{3-piperidin-1-carboflyl)-4-[( 4 trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyllacetoxymethyl)-malonic acid diethyl ester, {3-dimethylcarbamoyl-4- (4 '-trifluoroniethyl- Vn biphenyl- 2-carbonyl) -amino -phenyl) -acetic acid 2-phenyl-2o propionylamino-ethyl ester, {3-dimethylcarbamoyl-4-[1(4' -trifluoromethylbiphenyl- 2-carbonyl) -amino] phenyl}-aceti-c aciLd 2- dioxo-pyrrolid'in-1-yl) -2-phenyl-ethyl ester, (3-dimethylcarbaxnoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetic acid 2-ethylcarbamoyl-benzyl ester, {3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -pheny1J)-acetic acid 2-ethylcarbamoylmethyl-benzyl ester, {3-dimethylcarbanoyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 2-isopropylamino-2-phenyl-ethyl ester hydrochloride, 2- (2-(3-dimethylcarbaioyl-4- -trifluoromethylbipheriyl-2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2phenyl-nialonic acid diethyl ester, 2-(2-{3-dimethylcarbamoyl-4-[(4'-fJ-uoro-biphenyl-2carbonyl) -amino) -phenyl)-acetoxymethyl) 2-phenyl-malonic acid diethyl ester, (4'-bromo-biphenyl-2-carbonyl)-aminol-3dimethylcarbamoyl-phenyl-acetoxyfethYl) -2-phenyl-malonic acid diethyl ester, (3-dimnethylcarbamOyl-4- -tri-fluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2-acethylamino-2-phelyl-etlYl ester, 0 5 (3 -dimethylcarbanoyl- 4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 00 2-butyrylamino-2rpheflYl-ethyl ester, 2-(2-{3-dimethylarbamfl-4- -trifluoromethylo ~biphenyl-2-carbOlYl) -amino] -phenyl)-acetOxYlfethYl) 2-phenyl-maloliC acid dimethyl ester, 2-ylpny--2(-~ehlabmy--(' trifluoromethy-biphelyl-2-CarbOlYl) -amino] -phenyl)-' acetoxymethyl) -malonic acid diethyl ester, 2-cyclohexyl-2-(2-{3-dimethiCarbamToyl- 4 4 trifluoromethyl-biphelYl-2-carbonYl) -amino] -phenyllacetoxymethyl)-ialoliC acid diethyl ester, 2-2(-('clr-ihny--abnl-m~o-3 dimethylcarbamoyl-pheflyl}-aCetOXYmethYl) -2-phenyl-malolic acid diethyl ester, 2-21-('aey-ihny--abnl-mn]3 dimethylcarbamOyl-phelyl-acetoxymnethyl) -2 -phenyl-malonic acid diethyl ester, 2-2{-('caobpey--abnl-mn]3 dimethylcarbamoyl-phelyl) -acetoxymnethyl) -2 -phenyl-malonic acid diethyl ester, 2- (2-{3-dimethylcarbanOYl-4- [(4-methyl-C trifluromethyl-biphelYl-2-carbonyl) -amino) -phenyl)acetoxymethyl)-2-PhelYl-malOlic acid diethyl ester, 2-(2-{3-dimethylcarbamoyl-4-[(5methyl- 4 trifluromethyl-bip-helyl-2-CarbOlYl) -amino] -phenyl)acetoxymethyl)-2-pelYl-malOflic acid diethyl ester, Mn {3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid o ~5 2-methanesulfOlylamiflo-2-PheflYl-ethYl ester, 3- (2-{3-dimethylcarbamOyl-4- -trifluorornethyl- 00 biphenyl-2-carbOlYl) -amino] -phenyl)-acetosy) -2-phenyl- S) propionic; acid ethyl ester, {3-dirnethylcarbafOyl-4- '-trifluoromethylbiphenyl- 2-carbolyl) -amino]I -phenyl) -acetic acid 2- (methylpropionyl-amiio) -2-phenyl-ethyl ester, 2-[3-(2-{3-dimethylcarbaloYl-4-[ (4'-trifluromethyl- -biphenyl-2-carbOlYl) -amino] -phenyl)-acetOXY) -propyl]-2phenyl-malonic acid diethyl ester.

2-2(-iehlabmy--(-ehx-' trifluromethyl-biphel-2-CarbOlYl) -amino] -phenyl)acetoxynethyl)-2-PhelYl-falOflic acid diethyl ester, 2- [(5-chloro-4'-.trifluoromethy1-biphefl-2carbonyl) -amino] -3 -dimethylcarbamoyl-phelYl) acetosymethyl)-2-phelYl-malOlic acid diethyl ester, 2-(2-{3-dinethylcarbafoYl-4-[(6-methyl-4' trifluoromethyl-bphenyl-2-Carbol) -amino] -phenyl)acetoxyrnethyl)-2-phelYl-malolic acid diethyl ester, 2- (2-{3-dimethylcarbamnoYl-4- -trifluoroinethyl- -biphenyl-2-carbOl)-amino] -phenyl)-acetoxyfethYl) -2phenyl-maloflic acid di-2, 2, 2-trifluoroethYl ester, 2- (2-{3-dimethylcarbafoyl-4- -fluoro-4' trifluoromethyl-biphenYl-2-carbolYl) -amino] -phenyl}acetoxymethyl)-2-phelYl-malolic acid diethyl ester, 2-(2-{5-dimethylcarb8JlY-2-f1UOrO- 4 4 trifluorometbyl-biphefyly>2-CabonYi) -amino] -phenyl} acetoxymethyl)-2-phflyl-faloliC acid diethyl. ester, 2-(2-{3-brono-5-dimethyJ.carbwnfoyl- 4 4 o 5 trifluoromethY1-biPhnflY>2-CabolYl) -amino] -phenyl)lacetoxymethy)-2-PhelfalOfliC acid diethyl ester, 00 V trifluoromethyl-biphelyl-2-CarbOlyl) -amino] -phenyll 0 o acetoxymethyl)-2-PhelYl-faI~liC acid diethyl ester:- 2-(2-{3-dimethy1carbaoyl-y4(3-fluoro- 4 trifluoromethyl-biphelyl 2-carbonyl) -amino] -phenyl) acetoxynethyJ-)-2-PheflYl-malolic acid diethyl ester, 2- -chloro-4' -trifluororfethyl-biphny carbonyl) -amino] -3-dimethylcarbamOY1-PhenYl)h acetoxymethyl)-2-Phel-aloliC acid diethyl. ester, 2- (2-{3-dimethylcarbflOYl-4- -trifluorornetbylbiphenyl-2-CarbonYl) -amino] -pheny1)'-aCetoxyfethiYl) nitro-pyridin-2-yl)- malonic acid diethyl ester, 2-5aloprdn2y)2(-3dmtycraol 4- -trifluoromethyI-biphenY1-2-CarbOnYl) -amino] phenyl) -acetoxymethyl) -ialonic acid diethyl ester, 2- (2-{3-di-methylcarbafoyl-4-[ -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxymethyl) -2pyridin-2-y1-malOnic acid diethyl ester, 2-2(-hoo5dmtycraol2fur--(' trifluoromethyl-biphenYl-2carbonyl) -amino] -phenyl}acetoxyinethyl) -2-phenyl-malonic acid diethyl ester, 2-2{-rm--iehlcrwol2fur--(4'trifluoromethYl-biphenYl-2carbOfYl) -amino] -phenyl'acetoxymethyn-2-phehyl-malonic acid diethyl ester.

2-(2-{3-dimethy1Carbamfl-4-[ -trifluoromnethy1en biphenyl-2-carbOlYl) -amino] -phenylj'-aCetOXYTTethYl) -2-otolyl-nialoflic acid diethyl ester, o 2- (2-{3-dimethylcarbafOYl-4-[ -trifluoromethylbiphenyl-2-CarbOlYl) -amino]I -phenyl}-acetoxyflethyl) -2-mn- 00 tolyl-maloiic acid diethyl ester, 0) 2- (2-{3-dimethylcarbaTOY1-4-[ -trifluoromethylo ~biphenyJ--2-carbOflYl) -amino] -phenyl}-acetOXYmfethYl) -2-ptolyl-maloflic acid diethyl ester, 2-(2-chi-oro-phelyl) -2-(2-{3-dimethyCarbamylO3-4- -trifluorornethy1.biphenflY>catbOflYl) -amino] -phenyl)acetoxymethyl)-nalOliC acid diethyl ester, 2-3clr-hnl--2-3dmtycraol4 -trifluorornethy1-biphel-2-carbOlYl) -amino] -phenyl 1acetoxymethyl-nalolic acid diethyl ester, 2-4clr-hnl--2f-imtycraol4 '-trifluorornethyJl-biphefl-2-crbOlYl) -amino] -phenyl)acetoxymethyl)-nalolic acid diethyl ester, 2- (2-{3-dimethYlCarbamOYl-4- t(4' -trifluoromethylbiphenyl-2-carbOlYl) -amino] -pheny1}-acetOXYflnethYl) -2phenyl-succilic acid diethyl ester, 2- (2-{3-dimethylcarbamfoyl-4- -trifluorornethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-acetOXynethYl (2methoxy-phelyl)-laloflic acid diethyl. ester, .2-(2-{3-dimethylcarbatOyl-4- -trifluoromethylbiphenyl-2-carbOl) -amino] -phenyl)-&CtoxymlthYl) (3methoxy-phenyl)-falOliC acid diethyl ester, 2- (2-{3-dimethylcarbamoyl- 4 -trifluoromethylbiphenyl-2-carbolyl) -amino) -phenyl}-acetOXYmflthYl')-2-( 4methoxy-phenyl)-malOfliC acid diethyl ester, carbonyl) -amino]- 3-diinethylcarbaloyl-pheflyl) o 5 acetoxyrnethyl)-2-Phel-malOflic acid diethyl ester, 2-2{-(-hoo4-rfurmty-ihnl2 00 carbonyl) -amino] -3 -dimethylcarbanOyl-Phelyl) 0' acetoxymethyl)-2-phenyl-maloliC acid diethyl ester, o 2-(2-{3-dimethylcarbamhoy1-4-[(6-fluoro-'trifluoromethyl-biphelYl-2-CarbOlYl) -amino] -phenyl)acetoxynethyJ-)-2-PheflYl-maloflic acid diethyl ester, 2- (2-{3-dimethylcarbamnoyl-4- [(5-methyl-4' trifluoromethyl-biphenyl-2-CarbolYl) -amino I-phenylacetoxy) -ethyl] -2-phenyl-naloflic acid diethyl ester, 2-(2-{3-dimethylcarbamoyl4[(5ethoxCy- 4 trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl) acetoxyiethyl)-2-phelYl-falofliC acid diethyl ester, 2-(2-{3dimethyICarbafl-4-L (5-isopropoxy-4 trifluoromethyl-bip.SfYl- 2-carbonyl) -amino] -phenyl) acetoxymethyl)-2-PhelYl-malOlic acid diethyl ester, 2-2(-4(,'bstifurmty-ihnl2 carbonyl) -amino] -3-dimethylcarbamdyl-phelyl)I-acetoxy) ethyll-2-phenyl-malolic acid diethyl ester, 2- (2-{3-dimethylcarbaloyJ.-4- (6-methoxy-4' trifluoromethyl-biphefll2-carbolYl)-amino] -phenyl)acetoxymethyl)- -phenyl-maolic acid diethyl ester, 2- (2-{3-dimethylcarbamoYl-4- [(3-rnethyl-4' trifluoromethyl-biphelyl- 2-carbonyl) -amino] -pheny. Iacetoxymethyl)-2-PhelYl-maloflic acid diethyl ester, M cddity etr dimetbdietylcarbalfolPell maeoymethyl 2-hyl-ipnlfli 0 5 carbonyl) -amino] -phenyl)I-acetox-ynethyl) -2 -phenyl-maloniC acid diethyl ester, 2-{2-[3-dimethylcarba1Doy-4-U(2-ethyl-4trifuoromethy-beZOy2IBlaiflO)-phenyl] -acetoxymethyll -2o phenyl-malOrniC acid diethyl ester, carbonyl) -amino] -phenyl)-acetOxymfethYl) -2-phenyl-malolic acid diethyl ester, 2- (2-{3-diniethylcarbaflOyl-4-[I(4' -isopropenylbiphenyl-2-CabOlyl) -amino] -phenyll-acetOxyfethyl) -2phenyl-malOflic acid diethyl ester, 2- (2-{3-diniethylcarbamOyl-4- 1(4' -isopropylbiphenyl-2-carbolYl) -amino] -phenyll-acetoxyfethyl) -2phenyl-ma-OfliC acid diethyl. ester, [3-dirnethylcarbafOyl-4-t -trifluoromethylbi-phenyl-2-carbofllOXY)-phenyl] -acetoxyinethyl}-2phenyl-malonic acid diethyl ester, {3-dimethylcarbamfoyl-4- -trifluoronethybiphenyl-2-CarbOl) -amino] -phenyl)-acetic acid 2-ethyl- 2-phenyl-butyl ester, {3-dimethyJlcarbamoyl-4- -trifluoromethy.bipheny-2-CarbOl) -amino] -phenyl)-acetic acid 1-phenylcyciopropylmethyl ester, 3-dimethylcarbamoy.-4- -trifluoromethybiphenyl-2-carbOflyl) -amino] -phenyl)-acetic acid 2,2diphenyl-ethyl ester, (1)(3-dimethylcarbanOyl-4- '-trifluoromethylen biphenyl-2-carbolyl) -amino I-phenyll-acetic acid 1 -phenylcyclopentylmethy- ester, (3-dimethylcarbaDOy-4- -trifluoromethYlbiphenyl- 2-carbonlY) -amino] -phenyl)l-acetic acid 3-hydroxy- 00 2 -hydroxymethyl- 2-phenyl-propyl ester, 0 (3-dimethylcarbamoyl-4- F-trifluorcnnethYlci biphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 3-acetoxymethy1-2-phel-PrOPYI ester, 2-(2-{3-dimethylcarbamOYl-4-[1(4' -trifluorometbylbiphenyl-2-carbol) -amino] -phenyl}-acetOxYmethYl] -2thiophen-2-y-malOfliC acid diethyl. ester, 2- (2-(3-dimethylcarbamfl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetoxymethyl] -2thiophen-3-Y1-malOfliC acid-diethyl ester, 2- (2-{4-dimethylcarbd noyl-5- -trifluoromethylbiphenyl-2-carbolyl) -amino) -pyridin-2-yl-aCetOX-yflethYl)- 2-phenyl-malolic acid diethyl ester, 2-(2-(3-dimethylcarbamOYl-4-[ -trifluoromethylbiphenyl-2-OarbOlYl) -amino] -phenyl)-acetOxym~ethYl>-2-(3methy1-thiophen-2-Yl) -malonic acid diethyl 'ester, 2- (2-{3-dimethylcarbaloyl-4- -trifluoromethylbiphenyl-2-carbOlYl) -aiino] -phenyl)-acetoxymflthYJ-h-2- methyl-thiophen-2-y-)-falOflic acid diethyl ester, 2- (2-{3-dimethylcarbamOYl-4- -trifluoromethylbiphenyl-2-carbolYl) -amino] -pheny2l}-acetOXylethYJl)-2thiazol-2-yl-faloflic acid diethyl ester, 2-(2-{3-ethoxy-4-[ (4'-trifluoromfethyi-biPhenfl-2- CI carbonyl) -amino] -phenyll -acetoxymethyl) -2-phenyl-malolic O acid diethyl ester, {3-hydroxy-4- -trifluoromethy1-biPhenfl-2carbonyl) -amino] -phenyl)-acetic acid 2 ,2-biso 5 ethylcarbamoyl-2-pheflYl-ethYl ester {3-methoxy-4- -trifluoromethyl-biphelyl-2carbonyl)'-amino] -phenyl) -acetic acid 2 ,2-bis- S ethylcarbamoy.- 2 -phenyl-ethyl ester 2-(2-{3-methoxy-4-[(4'-trif1uoromethyl-biphenyl- 2 carbonyl) -amino] -phenyll-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, (3-methoxy-4- -trifluoromethyl-biphelYl-2carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2 ,2-bispropylcarbamoyl-ethyl ester, {3-methoxy-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyll-acetic acid 3. 3-bisethylcarbamoyl-"3-phenyl-propyl ester, {3-ethoxy-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyl)-acetic acid 2. 2-bisethylcarbamoy.-2 -phenyl-'ethyl ester, {3-etboxy-4- -trifluoromethyl-biphelyl-2carbonyl) amino] -phenyl)-acetic acid 3, 3-bisethylcarbanoy-3 -phenyl-propyl ester, 2-(2-{3-isopropoxy-4-[(4' -tritluoromethyl-biphelyl-2carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, {3-isopropoxy-4- 1(4' -trifluoromethyl-biphenYi-2carbonyl)-amino]-phelyll-acetic acid 2 ,2-bisethylcarbarnoyl- 2-phenyl-ethyl ester, {3-isopropoxy-4- -triLfluoromethyl-biPhefyl-2carbonyl)-aminO]-phenfl)-acetic acid 3,3-bisethylcarbamoyl- 3-pheriyl-propyl ester, (3-propoxy-4-[ -trifluoromethy1-biPhenfl- 2 carbony1)-amino]-PhelJ-aCetiC acid 2,2-bisethyloarbamoyl- 2-phenyl-ethyl ester, 00 {3-benzyJloxy-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyl)-acetic acid 2.2-biso ethylcarbamOyl-2-PhelYl-ethyl ester, 2-(2-{3-benzyloxy-4- -trifluorornethyl-bipheflyl-2carbonyl) -amino] -phenyll -acetoxymethyl) 2-phenyl-malolic acid diethyl ester, 2-2(-yrx--('tilooehlb-hnl2 carbonyl) -amino] -phenylll-acetoxymethyl) -2-phenyl-malolic acid diethyl ester, [3-methoxy-4- -trifluoromethyl-biPhelYl-2carbonyloxy) -phenyl] -acetoxymnethyl) -2 -phenyl-maloflic acid diethyl ester, 3-dimethylamino-4- -trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyll-aceti-c acid 2. 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, 3-piperidifl-1-yl-4- 1(4' -trifluoromethyi-biphelYl-2carbonyl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamoyl-2-PheflYl-ethyl ester, {3-pyrrolidin-1-yl-4- -trifluoromnethyl-biPhelyl- 2- carbonyl)-amino]-pheflyl)-aCetiC acid 2,2-bisethylcarbamoyl-2-PheflYl-ethYl ester, 2-phenyl-2-(2-{3-piperidifl-1-Yl-44 trifluoromethyl-biphenyl-2-CarbOlYl) -amino] -phenyl)acetoxymethyl)- inalonic acid diethyl ester, en trifluoroznethyl-bipheflYl-2-CarbOlYl) -amino] -phenyl)acetoxyinethyl)- malonic acid diethyl ester, o 2-(2-{3-dimethylamilO-4-[ (4'-trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyll-acetoxymethYl) -2- 00 '4 phenyl-malonic acid diethyl ester, o ~biphenyl-2-carbOrlYl) -amino] -phenyl}-acetOXymlthYl)-2phenyl-malolic acid diethyl ester, 2- (2-{3-dethyalilO-4-[ -trifluorornethylbiphenyl-2-carbonyl) -axninol -phienyll-acetoxymethyl) -2phenyl-malonic acid diethyl ester, 2-2(-2mty--('trfurmty-ihnl2 carbonyl) -amino] -phenyll-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-{.3-[ (4'-trifluorolnethyl-biPherlyl-2carbonyl) -amino]I -phenyl) -acetoxynethyl) -malonic acid diethyl ester, 2-phenyl-2- 1(4' -trifluoroniethyl-biPheflYl-2carbonyl) -amino] -phenyll-acetoxy) -ethyl) -malonic acid diethyl ester, -trifluoromethyl-biphelyl-2-carbolYl) -amino] phenylil-acetic acid 3, 3-bis-ethylcarbamoyl-3-Phell propyl ester, -trifluoromethyl-biphenyl-2-CarbOlyl) -amino] phenyl)-acetiC acid 3-phenyl-3 ,3-bis-propylcarbafoylpropyl ester, carbonyl) -amino) -phenyl)-acetory) -ethyl-2-phel-TalOfliC acid diethyl ester, 2-methyl-5-[ (4'-trifluoronethyl-biphel-2carbonyl) -amino] -phenyl) -acetoxy) -ethyl] -2 -phenyl-malonic acid diethyl ester, -trifluoromethyl-biphenyl-2-CarbOlYl)-amino] phenyl)-acetic acid 3, 3-bis-isopropylcarbamOYl-3phenyl-pr opyl ester, {2-rnethyl-3-[ -trifluoromethyl-biPhelYl-2carbonyl) -amino) -phenyll-acetic acid 3, 3-bisethylcarbamoyl-3 -phenyl-propyl ester, {2-methyl-3- -trifluorornethyl-biPheflYl-2carbonyl) -amino] -phenyl)-acetic acid 4, 4-bisethylcarbamoyl- 4-phenyl-butyl ester, (2-methyl-3- -trifluoromethyl-biphelYl-2carbonyl) -amino] -phenyl)-acetic acid 3-phenyl-3 ,3-bispropylcarbainoyl-propyl ester, (2-methoxy-3- -trifluoromethyl-bipheflyl-2carbonyl) -amino) -phenyl)-acetic acid 3, 3-bisethylcarbamoyl-3-phelyl-PrOPYl ester, 2-12-(2-{2-methoxy-3-[(4'-trifluorometby1-biphenYL' 2-carbonyl) -amino] -phenyll-acetoxy) -ethyl] -2-pheflylmalonic acid diethyl ester, {2-ethoxy-3- -trifluoromethyl-biphelyl- 2 carbonyl) -amino] -phenyll-acetic acid 3, 3-bisethylcarbamoyl-3-phelYl-Propyl ester, 2-j2-(2-{2-ethoxy-3-[(4'-trifluoromethy1-biphel-2carbonyl) -amino] -phenyl)-acetoxy) -ethyl) -2-phenyl-malonic acid diethyl ester, 5biphenyl-2-carbOrlYl) -amino] -phenyll-acetoxy) -ethyl) -2phenyl-maloflic acid diethyl ester, o biphenyl-2-carbOlyl) -amino) -phenyl)-acetOXY) -ethyl) -2phenyl-maloflic acid diethyl ester, 00 4-('tilooehbiphenyl-2-Cabf~)-mn]-hnl- coy) etyl -2oo penylmai Oi acid iey2-abnlamo]ethyl ester, 4- -trifluoromethYl-biPel-2-'CarbOnYl) -amino) benzoic acid 2-(2(biphenyl-2-aeyl amino] -ethyl ester, 4- -trifluoromethy1-biphenyl-2-CarbOnyl) -amino] benzoic acid 3-naphthalef-1-Yl-3-(2, 2 ,2trifluoroethylcarbalOyl) -propyl ester, 4- '-trjfluoromethyl-biphenyl-2-carbOnyl) -amino) benzoic acid 3-[2-(2,2,2-trifluOroethylcarbam~oYl) -naphthalen-l-yl] -propyl ester, 4- -trifluoromethy1-bipheW1-2-carbonyl) -amino) benzoic acid 3, 3-dipheflyl-3- 2,2-trifluoroethylcarbaIOYI) -propyl ester, 4- -trif2luoromethyl-biphenyl-2-carbolYl) -amino) benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoroethylcarbaxnoyl)-proPYl ester, 4- -trjfluoromethyl-biphenyl-2-CarbonYl) -amino] benzoic acid 3-pheny1-3-(2,2,2-trifluoroethylcarbafoyl) -propyl ester, 4- '-trifluoromethyl-biphenyl-2-CarbOnyl) -amino) benzoic acid 2- 2-trifluorO-6thycarbJfOYl) naphthalen-1-yl]-ethyl ester, 4- -trifluoromethyl-biPhelYl-2-CarbOlYl) -amino] benzoic acid 3-(2,6-dichloro-pheflyl)-3-(2,2,2-triflUOroo 5 ethylcarbamoyl)-prOPYl. ester, F trifluoromethy1-biPheflYl-2-CarbOnYl) -amino] 00 '4benzoic acid 3-2clr-hnl--222tiloo S) ethylcarbamOyl)-prOPYl ester.

carbonyl) -amino] -benzoyloxy)-ethYl) -malonic acid diethyl ester, 2-(2-{3-methyl-4-[ -trifluoromethyl-biPhefYl-2 carbonyl) -amino] -benzoyloxyl -ethyl) -2-phenyl-malOflic acid diethyl. ester, 2- (2-{2-chioro-4- -trifluoromethyl-biphenWJl- 2 carbonyl) -amino] -benzoyloxy}-ethYl) -2-phenyJ.-maloflic acid diethyl ester, 2-hnl2{-4('tifurmty-ihnl2 carbonyloxy) -benzoyloxy] -ethyll-naloflic acid diethyl ester, 4- -trifluoromethyl-biphel2-ca1bOl)-amino] benzoic acid 3, 3-bis-ethylcarbaly-3-Phefl-PrOPYl ester, 4' -trifluoromethyJ-biPhefylY2carbOxcYlic acid (3,3bis-ethylcarb8IfOyl3-pheflYl-PrOPOxcacbonYl) -2-chiorophenyl ester, 4' -trifluoromethYl-biPhelYl-2-carbOxcylic acid* 4- 3 -bis-ethylcarbamoflOY3-Phel>PrOPO)CycarbonrYl) -phenyl ester, 4, -trifluoronethyl-biPheflYl-2-CarbOXYlic acid 4- (3,3bis-ethylcarbamflYI3-pheylY>propoxycarbonYl) 6-dichloro-p henyl ester, 0 2-(2-C3-ethoxycarbOflyl-4- -trifluoromethybiphenyl-2-carbolYl) -amino] -phenyl)-acetoxymethYl) -2phenyl-malonic acid diethyl ester, o 2- (3-{3-disnethylcarbamfoyl-4-[ (4 -trifluoromethylbiphenyl- 2-carbonyl) -amino] -phenyl) -propionyloxymethyl) 00 '4 2-phenyl-nialoniC acid diethyl ester, 0' 3-13- -trifluoromethyl-biphelyl-2-CarbonY.) 0 amino] -phenyl)-propiolic acid ethylcarbamoyl-phelmethyl ester, 2-bis-ethylcarbamoyJ-2-PhefYl-ethOXYCarhOflYlmethyl) -trifluoromethyl-bi~heflYl-2CarbOlYl) amino] -benzoic acid benzyl ester, 2-bis-ethylcarbamfoyl2-pheyl-lethOXYCarboflYlmethyl) -trifluoromethy1-biPhelyl-2-CarbOlYl) axnino]-benzoic acid, 2-bis-ethylcarbamOyl-2-phelYl-ethOXYCarbOlYlmethyl) -trifluoromethyl-biPhelyl-2-Carbolyl) amino]-benzoic acid ethyl ester, 2, 2-bis-ethylcarbamOyl-2-phelyl-ethoxycarbolmethyl) -trifluoromethyl-biphenyl-2-arbolyl) aminol-benzoic acid methyl ester, 2- (2-(3-benzyloxycarbOlyl-4- -trifluoromethylbiphenyl-2-carbolYl) -amino] -phenyl}-acetoxynethyl) 2-phenyl-malOrlic acid diethyl ester, 2- (2-(3-carbOxcy-4- '-trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyl)-acetox-ymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-{3-isOprOpOXYcarbofYl-44 -trifluoromethylbiphenyl-2-carbonyl) -amino] -pheny1)-acetOx-ymethYI) -2phenyl-nialoflic acid diethyl ester, Cr) 2- (2-{3-methoxyCarbOflYl- 4 -trifluoroinethylbiphenyl-2-carbOlYl) -amino) -pheny1}-acetoxytmethyl) 2o ~5 phenyl-maloflic acid diethyl ester.

2-2(-ctlmn--('tilooehl 00 '4 biphenyl-2-carbOlyl) -amino) -phenyJ'-aCetoxymfethYl) 0 2-phenyl-maloliC acid diethyl ester, o (2-f 3-methoxycarbonylamino-4- -trifluoroinethylbiphenyl-2-CarbOlYl) -amino] -pheny1)-aCetoxyflethYI) 2phenyl-malolic acid diethyl ester, 2-2(I(-ehl-hao-2y)4[(4'trifluoromethyl-biPhelyl- 2- carbonyl) -amino] -phenyl) acetoxymethyl)- 2-phenyl-maloflic acid diethyl ester, 2-hnl(-6[4-rfurmty-ihnl2 carbonyl) amino] .bphenyI -3 -y11-acetOXYmfethYl) rnalonic acid diethyl ester, 2-21-oml4[4-rfurmty-ihnl2 carbonyl) -amino] -phenyl}-aCetOXYmflthYl) -2-phenyl-m&LaliC acid diethyl. ester, 2- (2-f 3-dimethylafiflOmethy1- 4 -trifluoroinethylbiphenyl- 2- carbonyl) -amino] -phenyl) -acetoxyinethyl) -2 phenyl-maloniC acid diethyl ester, 2- 2-{3(methoxy-methylcarbaWOYl) trifluoromethyl-biPhenyl- 2- carbonyl) -amino I-phenyl) acetoxymethyl) -2-phenyl-maloflic acid diethyl ester, 2- (2-f 3-isobutyryl-4,-[(4' -trifluoromethy3.-biphenYl- 2-carbonyl) -amino] -phenyll-acetoxymetbYl) -2-phenyl-malonic acid diethyl ester, and trif luoromethyl-biphelyl-2-Cc-rbOlYl) -amino]I -phenyl) MC acetoxymethyl)-2-PhenflY-alolic acid diethyl. ester; o 5 (25) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the 00 '4 above which is selected from the group consisting of 0' trifluoromethyl-bipheflYl-2-carbonYl) -amino] 0 phenyl)-acetic acid 2, 2-bis-ethylcarb81Toyl-2-Phenfl-ethYl ester, {3-ethyl-4- -trifluoromethyl-biPhenyl- 2 carbonyl) -amino] -phenyl}-acetic acid 2, 2-bisethylcarbamnoyl-2-pheflYl-ethYl ester, -trifluoromethyl-biphelyl-2-carbolYl) -aiinolphenyl)-acetic acid 2-phenyl-2,2-bis-(2,2,2-trif1uoro- -ethylcarbamoyl) -ethyl ester, -trifluoromethy-biphelYl-2-carbolYl) -alino] phenyll-acetic acid 2. 2-bis-cyclohexylCarbamoyl-2phenyl-ethyl ester, -trifluoromethyl-biPheflYl-2-carbolYl) -amino] phenyl)-acetic acid 2-phenyl-2 ,2-bis-phenylcarbaloylethyl ester.

-trifluoromethyl-biphenyl-2-carbOlyl) -amino] phenyl)-acetic acid 2 ,2-bis-isopropylcaramoyl-2-Phelethyl ester, 4' -trifluorornethy1-bipheflyl-2-carboxylic acid 4- [2phenyl-2, 2-bis- 2-trifluoro-ethylcarbamoyl) ethoxycarbonyllethyl] -phenyl ester, biphenyl-2-catboxylic acid 4- [2-phenyl-2 ,2-bis- 2-trifluoro-ethylCarbafOyl) -ethoxycarbonytmethyl] phenyl ester, en (biphenyl-2-crbOflyl)-amil]-phenyl}-acetic acid 2-phenyl-2, 2-bis- 2-trifluoro-ethylcarbfloyl) -ethyl ester, 2-phenyl-2-(2-{2-triflUOrOflethYl' 4 -t 00 trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl) o acetoxymethyl)-malofliC acid diethyl ester, 0 -trifluoroznethyl-biphenYl-2-CarbOlYl) -amino]p henyl)-acetic acid 2, 2 -bis -methylcarbamOY- 2-pheyl-ethyl ester, 4'-~triflucromethyJ.-biphefyly-2-CarbOXYliC acid 4-(2 .2bis -ethylcarbamoyl- 2-phenyl-ethoxycarbOflmfethYl) -phenyl ester, -trifluoromethyl-biphelyl-2-CarbOlYl) -amino] phenyl)-acetic acid 2, 2-bis- bntylcarbanioyl-2-Phefl-thYlester, {3-methyl-4- '-trifluoromethyl-biPheflYl-2carbonyl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbamoyl-2-phenYl-ethYl ester, -trifluoromethyl-biphelyl-2-Carbolyl) -amino] phenyll-acetic acid 3. 3-bis-ethylcarbamoyl-3-Phel-PrOPYl ester, -trifluoromethy-biPhelYl-2-CabOflYl)-amilO] phenyii-acetic acid 3-phenyl-3, 3-bis-propylcarbafOyl-prOPYl ester, {4-[t(biphenyl-2-carboflyl)-ahilo] -phenyll-acetic acid 2, 2-bis-ethylcarbafloyl-2-phelYl ethyl ester, 4' -trifluoromethyl-biphelYl-2-carboxCyliC acid 4- (2,2bis-ethylcarbaioyl- 2-phenyl-ethoxycarbOflfetlYl) -2 -chiorophenyl ester.

[(4'-.trifluoromethy1-biphefl2-CarboflYl) -amino] phenyl)-acetic acid 2,2-bis-isobutylcarbamOY2.-2-PhelYl ethyl o 5 ester, -trifluoronethy1-biPhelYl-2-C6XbOflYl) -amino] 00 phenyl}-acetic acid 2, 2-bis- (3-methyl-butyCarb~Ifoyl) -2- S phenyl ethyl ester, {4-t (4'-chlorobiphenyl2-CarbOYl)-aifOliphefll acetic acid 2,2-bis-ethylcarbamfOYl-2-PheflYl ethyl ester, (44 ,4'-dichloro-biphelyl-2-CarboflYl)-amfiflO] phenyl)-acetic acid 2, 2-bis-ethylcarbamO~l) -2-pheriyl-ethyl ester, {3-methyl-4- [(4'F-trifluoromethyl-biphenyl2carbonyl) -aminoII-phenyl}-acetic acid 2-phenyl-2 ,2-bispropylcarbanioyl)-ethYl ester, -trifluoromethy-bipheiyl-2-CarbOlYl) -amino] phenyl)-acetic acid 2, 2-bis- (2-methoxy-ethYlcarbalOyl) 2-phenyl-ethyl ester, 3-isopropyl-4- -tritluoromethyl-biphelyl-2carbonyl) -amino) -phenyl)-acetic acid 2, 2-bisethylcarbamoyl-phenl-thyl ester, (3-ethyl-4- -trifluoromethyl-biPhelyl-2carbonyl) -amino] -phenyl)-acetic acid 3, 3-bisethylcarbamoyl-3-phelyl-PrOPYl ester, {3-isobutyl-4- -trifluoromethyl-biphelyl-2carbonyl) -amino) -phenyl)-acetic acid 2. 2-bisethylcarbaxfOyl-2-Phefl-ethYl ese, {3-dimethylcarbamoYl-4- -trifluoromethylbiph'enyl-2-carbOlyl) -ami-no]I -pheniyl} -acetic acid 2 -phenyl- 2, 2-bis-propylcarbamOY1-ethYl 'ester, mn (3 -nethylcarbamoyl- 4-11(4'-~trfluoromethY1-biPhefl 2-carbonyJ.)-amifl-phenfl1>'cetic acid 2 ,2-biso 5 ethylcarbamoyl-2-Phenfl-lthYl ester, {3-dimethylcarbafoYl-4- 11(4' -trifluorornethyl-biPhelyl- 00 2 2- carbonyl) -amino]-phenyl}-acetic acid 3, 3-biso ethylcarbamoyl-3 -phenyl-propyl ester, 0 ~(3-benzylcarbamOYl-4-[1(4'-~trifluoromethy1-biPhel- 2 carbonyl) -amino]-phenyl}-aCetiC acid 2 ,2-bisethylcarbanOyl- 2-phenyl-ethyl ester, 3- dimethylcarbamoyl triluoromethyl biphenyl-2-carbOflYl) -amino] -phenyll--acetic acid 4, 4-bisethylcarbaroyl-4-phenfl-bUtYl ester, 3-diethylcalrbamoyl-4-1(4' -trifluoromethyl-biphelyl- 2-carbony)-amlirio]-phefyl1-acetic acid 2,2-bisethylcarbalOyl- 2-phenyl-ethyl ester, (3-diisopropylcarbamOyl-4- -trifluoromethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2, 2-bisethylcarbaifoyl-2-PheflYl-ethYl ester, 3- (isopropyl-nethylcarblfoyl) triiluoromethyl-biphelyl-2-CarbOflYl) -amino] -phenyl)- acetic acid 2, 2-bis- ethylcarbamoyl-2-pheflyl-ethyl ester, (ethyl-methylcarbal) -trifluorometllylb~iphenyl-2-carbolyl)-aminlo]-phenyl)-acetic acid 2,2-hisethylcarbamoyl- 2-phenyl-ethyl ester, (ethyl-methylCarbamoyl) -4-11(4' -trifluorometbylbiphenyl-2-carbOlYl) -aminol -phenyl)-acetic acid 3, 3-bisethylcarbamoyl- 3-phenyl -propyl ester, (piperidif-l-CarbOlYl)-4- -trifluoromethylbiphenyl-2-CarbOlYl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbamoy1-2-pheflethYl ester, (3-(pyrrolidin-l-Carbolyl) -trif luor'nethylbiphenyl-2-carbOlyl) -amino] -phenyll-acetic acid 2 ,2-bisethylcarbamOyl-2-Pheflyl-ethYl ester, (methyl-prOpylCarbamfoyl) -trifluoromethylbiphenyl-2-carbolYl) -amino] -phenyl)-aCetic acid 2,2-hisethylcarbanoyl- 2-phenyl- ethyl ester, (methyl-propylarbamfl) -trifluoromethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-acetiC acid 3 ,3-bisethylcarbanOyl- 3-phenyl -propyl ester, {3-hydroxy-4- -trifluoron'8thY1-biPheflYl- 2 carbonyl) -amino) -phenyl}-acetic acid 2. 2-bisethyl carbamfOyl- 2-phenyl-ethyl ester, (3-methoxy-4- -trifluorotnethyl-biPhefYl-2 carbonyl) -amino] -phenyl)-aCetiC acid 2 ,2-bisethylcarbaflOyl-2-phefyllethYl ester, {3-methoxy-4- -trifluorOmfethy1-biphefll 2 carbonyl) -amino] -phenyll-acetic acid 2-phenyl-2 .2-hispropylcarbamoyl-ethyl ester, (3-methoxy-4- -trifluoromethy1-biphefll 2 carhonyl) -amino] -phenyll-acetic acid 3, 3-hisethylcarbamOyl-3-PheflYl-PrOPYl ester, (3-ethoxy-4- -trifluorornethyl-biphefll 2 carbonyl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbamoyl-2-pheflyl-ethYl ester, {3-ethoxy-4- -trifluoromethy1-biPhelYl- 2 carbonyl) -amino] -phenyl)-acetic acid 3 ,3-biLsethylcarbamoyl- 3-phenyl-propyl ester, {3-isopropoxy-4- [(4'-~trifluoromethY1-biPhefl 2 encarbonyl)-amnl]-phenyl)-acetic acid 2 ,2-bisethylcarbamoyl- 2-phenyl-ethyl ester, o 5 {3-isopropoxy-4- 1(4' -trifluoromethY1-biPhenYI-2carbonyl)-anfO] -phenyl)-acetic acid 3 ,3-bis- 00 ethylcarbamoyl phenyl -propyl ester, 0) (3-propoxy-4- trifluoromethy1-biPheflYl- 2 0carbonyl) -amino] -phienyl)- acetic acid 2, 2-bisethylcarbamoyl-2-pheflYl-ethYl ester.

{3-benzyloxy-4- -trifluoromethyl-bipheflI 2 carbonyl)'amilOl-phenyll-acetic acid 2, 2-bisethylcarbainoyl- 2-phenyl-ethyl ester, (3-dirnethylamino-4- -trifluoromfethy-biphafylY carbonyl)-aminO] -phenyll-acetic acid 2,2-hisethylcarbamOyl- 2-phenyl-ethy. ester, (3-piperidin-1-yl-4- -trifluoromethY1-biphel- 2 carbonyl)-anll-phenyl)-acetic acid 2, 2-bisethylcarbamoyl- 2-phenyl-ethyl ester, {3-pyrrolidifl-1-yl-4- -trifluoromethyl-biphelYl- 2-carbony1)-amnino]-phefl>acetic acid2,-is ethylcarbamoyl-2-PhelYl-ethYl ester, -trifluoromethr1-biphelYl- 2-carbonyl) -amino] phenyl)-acetic acid 3, 3-bis-ethylcarbalY-3-Phefl-PrOPYl ester, -trifluoromethy1-biphel-2-CarbOnl) amilo] phenyl}-acetic acid 3-phenyl-3, 3-bis-propylcarbamoylpropyl ester, -trifluoromethy1-biPhefl-2CarbOnYl)I-amino] phenyl)-acetic acid 3, 3-bis -isopropylarbalOYl- 3- PhelYlpropyl ester, en (2-methyl-3- '-trifluoromethyl-biphelyl-2carbonyl) -amino] -phenyl)-acetic acid 3,3-biso ~5 ethylcarbamoyl-3-phelyl-prOPYl ester, {2-methyl-3- -trifluoromethyl-biphenyl-2- 00 carbonyl) -amino] phenyl)-acetic acid 4 ,4-bis- S) ethylcarbanoyl-4-phelyl-bfltyl ester, {2-methyl-3- -trifluorornethyl-bipheflyl-2carbonyl) -amino] phenyll-acetic acid 3-phenyl-3 ,3-l-ispropylcarbamoyl-propyl ester, {2-inethoxy-3- 1(4' -trifluoromethyl-biphelyl'-2carbonyl) -amino] phenyl)-acetic acid 3, 3-bisethylcarbaxnoyl-3-phenyl-PrOPYl ester, (2-ethoxy-3- '-trifluoromethyl-biphenyl-2carbonyl) -amino]I -phenyll -acetic acid 3,-3-bisethylcarbamoyl-3-phelYl-PrOPYI ester, 4- -trifluoromethyl-biphenyl-2-CarbOnYl) -amino] benzoic acid 3, 3-bis-ethylcarbaxnoyl-3-pheflyl-propyl ester, 4' -trifluoromethyl-biphenyJl-2-CarbOXyliC acid 3,3bis -ethylcarbanoyl- 3-phenyl-propoxycarboflyl) -2-chiorophenyl ester, 4 -trifluoromethyl-bipherlyl-2-carboxylic acid 4- (3,3bis-ethylcarbanoyl- 3-phenyl-propoxycarbonyl) -phenyl ester, 4' -trifluoromethyl-biphenyl-2-Carboxylic acid 4- (3,3bis-ethylcarbanoyl-3-phenyl-proPOXYcarbOflYl) 6-dichiorophenyl ester, 2, 2-bis-ethylcarbamnoy1-2-phel-ethOXycarbOlylmethyl) -trifluoromethyl-biphelYl-2 -carbonyl) axnino]-benzoic acid benzyl ester, 2-bis-ethylcarbaToyl-2-PhefYl-ethoxycarboflYlen methyl) [(4'-~trifluoromethyl-biPhel-2-CarbOlYl) amino] -benzoic acid, o 56 5- (2 ,2.bis-ethylcarbamoyl-2-Phefl-ethOxWCarbOlYlmethyl) -2-11(4'-~trifluoromethyl-biPhenYl-2-CarbolYl) 00 arnino]-benzoic acid ethyl ester, and 0 5- 2-bis-ethylcarbamoyl-2-pheflethOXyCrbolyl- 0 ~methyl) -trifluoromethyl-bipheflyl-2-CarbOflyl) axino)-benzoiC acid methyl ester; (26) The eater compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of 2-hnl2(-4('tifurmty-ihnl2 carbonyloxy) -phenyl I-acetoxyrnethyll -malonic acid diethyl ester, 2- (2-{3-methyl-4- [(4'-.trifluoroxethyJ-biPhenYl-2carbonyl) -amino] -phenyl)-acetoxynethyl) -2-phenyl-malonic acid diethyl ester, 2- [methyl- -trifluoromethyl-biphelyl-2carbonyl) -amino) -phenyl}-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-{4-[ -trifluoromethyl-biphelyl-2carbonyl) -amino -phenyl) -acetoxymethyl) -malonic acid diethyl ester, 2-phenyl-2- -trifluoroinethyl-bipheflyl-2carbonyl) -amino J-phenyl1- acetoxymethyl) -malonic acid diisopropyl ester, 2carbo l) -aminO -Pheny-aCetOXYf1tYl) -malonic ai en diethyl ester, 00 2-chylpet-2- (-{(4'-t[(4flrioro rnetliheY1-bihelY o 5 2carbonyl)-amino] -phenyl)-acetoxymflthYl) -malonic acid dietchyl ster, carbonyl) -amino] -phenyl)-acetox ymethy-) -malonic c idy 0 diyclheslteter 22en-12-(2y- 4 -t -trifluoromethy2--biphefyl-2 carbonyl) -amino] -pheny1)-acetoxymethYl) 2py-malonic i ity esterithl str 'triflrohy2--bihY1-- 2carbonyl) -amino -phenyl-acetOxYlethYl)--phen-BIc fli 1 acdiethyl ester, 2-cyclohex2yl-2-(-4- trifuoroethy-biPheY- 2-carbolyl) -amino] -phenyl)-acetoxynethYl) -malonic acid diethyl ester, 2-phein.-2l2-(2-rif1U(r'mthifluorm[C 4 2-hn--carbonyl) -amino -phenyl) -acetoxymethyl)- -rnaonic ai acdiethyl ester, 2-pheny1-2-(2-(3-trif1uoromfethy- 4 4 trifluoromethyl-biPhefyll2-carbOnyl) -amino] -phenyl)acetorymethyl) -malonic acid diethyl ester, 2-2(-('mty-ihey--abnl-mnl rn phenyll-acetoxymfethyl) -2-pheny1-ma1OfliC acid diethyl- ester, 2-(2-(4-[(4-ehx-ihnl--abnl-mn] phenyl1-acetoxymethY1)2-PhelYl-malonic acid diethyl ester, 00 carbonyl) -amino] I phenyl) -acetOXYmethYl) -Inalonic acid diethyl 0) ester, 0 [isopropyl-(4 -trif1uoromfethylbiphenyl>2 carbonyl) amino] phenyl) -acetOXyflflthYl) -2 -phenyl -falOfliC acid diethyl ester, 2- 2-C4- [cyclohesyl- -trifluoromethY1-biPheflYl-2 carbony))-amino] -phenyl) -acetosymethyl) -2-pheny-ma2lic acid diethyl ester, 2-phenyl-2-(2-t 4 -t (4'-trifluorOmfethY1-biPhefYl-2carbonyl) amino] -phenyl) -acetoxymethyl) -malonic aciddipropyl ester, 2-pheny2l-2- [(4'-.trifluoromethYl-biPhefyl-l> carbonyl) -amino] -pheny1)-aCetOXYmethYl) -ialonic acid diisobuty- ester, 2- (2-f 4- [ethyl- -trifluoromethYl-biPhel- 2 carbonyl) -amino] -pheny1}-acetOXYmflthYl) -2-phenyl-la-Oflic acid diethyl ester, 2-C 2-f 3-ethyl-4- -trifluorOmethyI-biPhel-2carbonyl) amino] phenyl) -acetOSYflethYl) 2- pheny-malOflic acid diethyl ester, 2- (2-{3-isopropyl- 4 -trjtiuoromethy1-biphelyl- 2 carbonyl) -amino] -phenyl)-actOXYmfethYl) -2-phenyl-malolic acid diethyl ester, 2-(2-{3-isobutyl-4- (4'-trifluorOmethY1-biPhefl- 2 carbonyl) -amino] pheny1-aCetOXYmethYl) -2-phenyl-malolic MC acid diethyl ester, carbony l) -amino) I phenyl) -aCetOXYmflthYl) -2-pheflmalOliC acid diethyl ester, 0' carbonyl) -amino] pheny1}-aCetOXYmthYl) -2-phenyl-malolic 0 acid diethyl ester, 2- 2-(3-dime thycarb amolO- 4 -trifl-uorOflethYlbiphenyl-2-CarbOflYl) -amino] -pheny1)-acetOXYmflthyl) -2phenyl-maloflic acid diethyl ester, 2--(2-{3-diethyCarbamfl- 4 -trifluoromethylbiphenyl-2-CarbOrlYl) -amino] -pheny1)-aCetOXYJmethYl.)-2phenyl-malofliC acid diethyl ester, 2- (2-{3-diisopropy1Carbamofl- 4 -trifluoromethylbiphenyl-2-carbOlYl) -amino] -pheny1}-acetOXYmfethYl) -2phenyl-malolic acid diethyl ester, 2- (ethyl-methylcarbafOyl) -4-11(4' -trifluoromethyl-bipheflYl-2-CarbOl)-amino] -pheny11-acetoxymethYl) 2-phenyl-malolic acid diethyl ester, (3-(pyrroldile-1-carbOflYl) -trifluoromethYlbiphenyl-2-CarbOl)-amino] -phenyl)-acetic acid 2, 2-bisethylcarbanoy-2-phenyl-ethyl ester, 2-hnl2(-3(yrldn--abnl--(' trif1uoromethYl-biPhenY> 2 -carbonyl) -amino] -phenyl) acetoxymethyl)-falOfliC acid diethyl ester,' 2-hnl2(-3(ieidn--abnl--(' trifluoromethY1-biPhenfl>>carbonYl) -amino] -phenyljacetoxymetiyl)-malonic acid diethyl ester, en methyl-biphenyl-2-CarbOlYl) -amino] -phenyl)-aCetOXY) ethyij-2-phelyl-lalofliC acid diethyl- ester, o 5 2 2 -t 3 -dimethy1carb8XfylOY4(4-trif luoromethyl> biphenyl-2-carbOflYl) -amino] -pheny1}-aCetO'CYmlthYl) -2- 00 phenyl-malOflic acid diethyl ester, o ~dimethylcarbamfoYl-phelYl) -acetoxymethyl) -2 -phenyl-malolic acid diethyl ester, 2- (2-{3-dimethyC8atbamfl-4-[(4' -trifluorOmethybiphenyl CarbOflYl) amino -phenyl)}-aCetOXYlnethYl) -2 phenyl-mfaloflic acid diethyl ester, 2-cyclopenty1-2-(2-{3-diffethyCabamoYl± 4 t trifluoromethY1-biPheflJ-2CarbonYl) -amino] -phenyl)Iacetoxymethyl)-ialOfliC acid diethyl ester, 2-ylhxy -211dmtycrbmy--(4' trifluoromethY1-biPhefl-2-carbonYl) -amino) -phenyl)acetoxymethyl)-lalOfliC acid diethyl ester, 2-2(-('clr-ihny--abnl-mn]3 dimethylcarbafoyl-Phefll -acetoxymethyl) -2 -phenyl-nialoniC acid diethyl ester, 2- [(4'-~acety1-bipheny1-2-carbOlYl) -amino]- 3-dimethycarbaml-Phel>acetOXYffethYl) -2-phenylmalonic acid diethyl ester, 2-2 -('caobpey--abnl-mn] 3-iehlabmy-hey)aeoyehl-2-phenylmalonic acid diethyl ester, 2-C 2-{3-dimethy1carbamolY4 [(4-methyl-4 triflnoromethyl-bipbenyl-2-CarbOflyl) -amino] -phenyl} acetoxymethy1)-2-pheny-maOliC acid diethyl ester, CC) 2-(2-{3--dimethylcarbamol-4-[(5-Ifethy- 4 trifluoromethyl-biphenyl -2 -carbonyl) -amino) -phenyl) o 5 acetoxymethyl)-2-phenyl-naloliC acid diethyl ester, 2-[3-(2-{3-dimethylcarbamOyl-4-[ (4'-trifluoromethyl- 00 biphenyl-2-carbonyl)-amil-phenyl)-acetoxy) -propyl] -2o) pheriyl-malonic acid diethyl ester, ci 2-(2-{3-dimethylcarbamoyl-4-[(5-methOXY- 4 trifluoroznethyl-biphenyl-2-CarbOlyl) -amino] -phenyl} acetoxymethyl)-2-pheny--maloniC acid diethyl ester, (5-chloro-4'-trifluoromethyl-biphelyl-2carbonyl) -amino] -3-dimethylcarbanoyl-pienyl)acetoxymethyl) -2 -phenyl-malonic acid diethyl ester., 2- (2-{3-dimethylcrbamfOyl-4- [(6-mfethyl-4'trifluoroniethyl-biphelYl- 2-carbonyl) -amino] -phenyl) acetoxymethy1)-2-phenyl-malonic acid diethyl ester, 2- (2-.3-dimethylcarbamoyl-4- [4 -trifluoromethylbiphenyl -2 -carbonyl) -amino] -phenyl1- acetoxyinethyl) -2phenyl-maloniLc acid di-2,2,2-trifluoroetbyl ester, 2- (2-(3-dimethylcarbamoyl-4- -fluoro-4' trifluoromethyl-biphenyl-2-carbOlyl) -amino] -phenyllacetox-yrethyl)-2-phenyl-malonic acid diethyl ester, 2- (2-{5-dimethylcarbamoyl-2-fluoro-4- trifluorornethyl-biphenyl-2-carbonYl) -amino] -phenyllacetoxymethyl)-2-phenyl-faloiic acid diethyl ester, 2-(2-{3-bromo-5-dimethylcarbafOyl-4- 1(4'trifluorornethyl-biphenyl-2-carbOlYl) -amino] -phenyl)acetoxymethyl)-2-pheny-nalonic acid diethyl ester, 2-(2.-{3-chloro-5-diethylCarbaloyl-4-I( 4 trifluoromethyl-biphelyl-2-CarbOlYl) -amino] -phenyl)en acetoxymethyl) -2 -phenyl-malonic acid diethyl ester, 2-(2-f3-dimethylcarbamnoy1-4-[(3'-f1uoro- 4 o 5 trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyll acetoxyrnethyli-2-phenyl-malOflic acid diethyl ester, 00 0 carbonyl) -amino] -3-di-methylcarbamOyl-PhelYl)- 0 acetoxymethyl) -2-phenyl-malOflc acid diethyl ester, 2- (2-f 3-dimethylcarbamlY-4- -trifluoroinethylbiphenyl-2-carbonyl) -amino] -phenyl)-acetoxymethY-) nitro-pyridin-2-yl) -malonic acid diethyl este'r, 2-5aioprdn2y)2(-3dmtycraol4 -trifluoromethyl-biphelyl-2-carbOlyl) -amino] -phenyl)acetoxymethyl)-maloliC acid diethyl. ester, 2-f 3-dimethylcarbanloyl-4- -trifluoromethylbiphenyl carbonyl) -amino]- phenyl1- acetoxymethyl) -2pyridin-2-y.-malolic acid diethyl ester, 2- (2 -f 3chloro-5-'dime thycarbaml-2-f lorO- 4 -trifluornnethy1-bphel-2-CarbolYl) -amino) -phenyl)acetoxynethyl)-2-phenyl-falOlic acid diethyl ester, 2-(2-(3-bromo-5-dimethy1carbamroy1-2-f1uoro- 4 -trifluoromethyl-biphenyl-2-carborlyl) -amino) -phenyl)acetoxymethyl)-2-phelyl-malOnic acid diethyl ester, 2-{3-dimethylcarbamoyl-4- -trifluoromethylbiphenyl-2-carbol) -amino] -phenyi)-acetoxymethyl) -2-otolyl-malonic acid diethyl ester, 2-{3-dimethylcarbafOyl-4- -trifluoromethylbiphenyl carbonyl) -amino] -phenyl I- acetoxymethyl) -2-intolyl-malolic acid diethyl ester, 2- -dime thylcarbdmoyl- 4 -trif luoromethylen biphenyl-2-carbOflyl) -amino] -pheny1)-acetOXYmflthY-) -2-ptolyl-malolic acid diethyl ester, -trifluoromethy1-bipheflL2-CarbonYl) -amino) -phenyl)- 00 acetoxymethyl)-malOliC acid diethyl ester, 0 trifluoromethY1-biphel12-CarbonYl) -amino] -phenyllacetoxymethyl)-falOflic acid diethyl ester, 2- (4-chioro-phenyl-2-(2-{3-dimethy1CarbamOYI- 4 -trif luoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl) acetoxymethy)-mlalOfliC acid diethyl ester, 2- (2-{3-dimethylcarbafOYl- 4 -trifluorOmethylbi-phenyl-2-CarbOlYl) -amino] -pheny1}-acetoxymetY-) -2phenyl-succilic acid diethyl ester, 2- (2-{3-dimethylarbamfoyl-4- -trifluoromethylbiphenyl-2-CarbOflYl) -amino] -phenyl)-acetoxyfethyl) (2methoxy-phenyl)-faL~liC acid diethyl ester, 2- (2-{3-dimethylcarbamOY].-4- -trifluorornethylbiphenyl-2-carbOl)-amino] -phenyl)-aCetOxYlfethYl) methoxy-phelYl)-laloniC acid diethyl este~r, 2- 2-(3-dimethylcarbamnOYl- 4 -trif luorOmethylbiphenyl-2-CarbonlYl) -amino) -phenyl}-acetOxYlfethYl) (4methoxy-phelyl)-malOflic acid diethyl ester, 2- -bis-trifluoromnethy1-biPhel-l 2 carbonyl) -amino 1-3 -dimethylcarbamOYl-PhelYl) acetoxynethyl)-2-phenyl-maloflic acid diethyl ester, 2- [(6-chloro-4' -trifluoromethyl-bipheflyl- 2 carbonyl) -amino) -3-dixnethylcarbalOYl-PhenflJacetoxymethy)-2-PheYl)-faOliC acid diethyl- ester, en 2-(2-{3-dimethylcarbamol-4-[(6-fluoro- 4 trifluoromety-biphel-2-arbOflYl) -amino] -phenyl) o 5 acetoxymethyl)-2-phelYl)-malOliC acid diethyl ester, 2 -[2-(2-{3-dimethy1carbamoylO-4[5-methYl- 4 00 trifluoromethyl-biphel-2-CarbOlyl) -amino] -phenyl} o acetoxy)-ethy1]-2-phel)-maOfliC acid diethyl ester, Ci 2-(2-{3-dimethylcarbamol-4-[(5-ethoxy- 4 trifluoromethy1-biPhefl-2-CabofYl) -amino] -phenyl} acetorymethy)-2-Phel)-lOlic acid diethyl ester, 2-(2-{3-dimnethylcarbamoyl-4-[ (5-isopropoxy- 4 trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl} acetoxymethyl)-2-pheny1)-malOfliC acid diethyl ester, 2-2(-4[54-i-rfurmty-ihnl2 carbonyl) -amino] -3-dimethycarbamlOY-P.8fl)}-acetory) ethyl]-.-phenyl-mfalOfliC acid diethyl- ester, 2-(2-{3-dimethylcarbamOyl- 4 (6-methoxy-4 trifluoromethyl-biphel-2-carbonyl) -amino] -phenyl) acetoxymethy)-2-pheYJ-malOliC acid diethyl ester, 2- (2-(3-dimethylcarbamfOyl-4- II(3-methyl-4' trifltioromethyl-biphelyl-2-CarbolYl) -amino] -phenyllacetoxymethyl)-2-phely-alolic acid diethyl ester, 2-2[-24bstilormty ezyaio-3dimethylcarbanloyl-phenYl] -acetoxymethyl)-2-phelyl) -malonic acid diethyl ester, 2- (2-f 3-dimethylcarbwlloyl-4- -methyl-biphenyl-2carbonyl) -amino] -pheny11-acetoxyflethYl) -2-pherlyl-maloflic acid diethyl ester, 2-f{2-[3-dimethyi-carbaxoy1- 4 d (2-ethyl-4-trifl'uorOmethy-benzoyainfl) -phenyl] .acetoxymethy11-2-Phenflen malonic acid diethyl ester, 2- (2-{3-dimethylcarbalOyl- 4 -ethyl-bipheny1-2o 5 carbonyl) -amino] -phenyl}-aCetOXYITethYl) -2-phenyl-malonic aci-d diethyl ester, 00 0 ~biphenyl-2-CarbOlYl) -amino] -phenyl)-acetOX7ymfethYl) -2- 0 phenyl-maloflic acid diethyl ester,.

2- (2-t3-di-methylcarbaDOY1- 4 -isopropyl-bipheiyl- 2-carbonyl) -amino,]-phenyl) -acetoxymethy-) -2-phenyl-malonic acid diethyl ester, 2-112- [3-dimethylcarbafoYl-4- -trifluoromethyl- -bipheny-2 -carbonyloxy) -phenyl] -acetoxyrnethyl)I- 2-phenylinalonic acid diethyl ester, 2-C 2-{3-di-methycarbamfOYl-4- -trifluoronethybiphenyl- 2- carbonyl,) -amino] -phenyl)I-acetoxyrnethyl) -2 thiophen-2-y-- malonic acid diethyl- ester, 2-(C2-{3-dimethylcarbaflOYl- 4 -trifluoromethylbiphenyl-2-carbolyl) -amino] -phenyJ.)-acetOXYrfethYl) -2thiophen-3-yl- malonic acid diethyl ester, 2-{4-dimethylcarbafoYl-5- -trifltoromethylbiphenyl-2-CarbolYl) -amino I-pyridin-2-yl-aCtOX-YTTethYl) 2-phenyl- malonic acid diethyl ester, 2-{3-dimethylcarbafloyl-4-[ -trifjluoromethylbiphenyl-2-carbolYl) -amino) -phenyl}-acetOxylnethYl)-2- (3methy1-thophefl-2-Yl) -mai-onic acid diethyl ester, 2-{3-dimethylcarbZl-4- -trifluoromethylbiphenyl-2-carbOflYl) -amino] -phenyll-acetoxymfethYl) -2-CSmethyl-thiophen-2-yl)-TalOliC acid diethyl ester, 2- (2-{3-dirnethylcarbamoy2l-4-[ -trifluoromethylen biphenyl-2-carbonyl) -amino] -phenyjj}-acetoxylethYl) -2thiazol-2-yl-mnalonic acid diethyl ester, o 5 2- (2-(3-ethoxy-4- -trifluoromethyl-bipherlYl-2carbonyl) -amino] -phenyl}-acetox-ymethyl) -2-phenyl-malonic 00 ci acid diethyl ester, o 2-(2-{3-methoxy-4-[ (4'-trifluoromethyl-biphenyl-2- Ci carbonyl) -amino] -phenyl)-acetosymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-(3-isopropoxy-4- -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-{3-benzyloxy-4- -trifluoromethyl-bipheflyl-2carbonyl) -amino] -phenyll-acetoxyethyl) -2-phenyl-malonic acid diethyl. ester, 2-(2-{3-hydroxy-4-(4'-trf1uoromethy-bipheny1>2 carbonyl) -amino] -phenyl}-acetoxyethyl) -2-phenyl-malonic acid diethyl ester, [3-rnethoxy-4- -trifluoromethyl-biphenyl-2carbonyloxy) -phenyl] -acetoxyrnethyll-2-phenyl-malOlic acid diethyl. ester, 2-pheny1-2-(2-{3-piperidifl-1-y1-4-[(4'-trif1uoromethyl-biphenyl-2-carbol) -amino] -phenyl) -acetoxymethyl) malonic acid diethyl ester, 2-phenyl-2-(2-{3-pyrrolidil-l-yl- 4 -trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyil)-acetoxymethyl) malonic acid diethyl ester, 2-{3-dimethylamino-4-[1(4' -trifluoromethylbiphenyl-2-carbonyl)I-amino] -phenyll-acetOxymethYl) -2phenyl-malonic acid diethyl ester, biphenl-2-carbOlyl) -amino] -phenyl)-acetOxymflthYl) -2o 5 phenyl-malolic acid diethyl ester, 2-(2-(3-diethyl-aminO-4-[ (4'-trifluoromethyl- 00 biphenyl-2-carbolyl) -amino] -phenyl)-acetOXymethYl) -2o' phenyl-malonic acid diethyl ester, carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-{3-[ (4'-trifluoromethyl-biPhelyl-2carbonyl) amino) phenyl)j-acetoxymfethyl) -malonic acid diethyl ester, 2-hnl2[-2f-('trfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -ialonic acid diethyl ester, 2-2(-4mty--('trfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2-2(-2mty--('trfurmty-ihnl2 carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2- (2-f 2-methoxy-3- 1(4' -trifluoromethyl-biphenyl-2carbonyl) -amino] -phenyl).-acetoxy) -ethyl] -2-phenylmalonic acid diethyl ester, 2- (2-f2-ethoxy-3- -trifluoromethyl-biphenyl-2carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, 2-o 2 2 2 isoPropo Y3-[(4trifuoromethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-aCetOXY) -ethyl) -2- M phenyl-malonic acid diethyl ester, (2-(2-methoxyCarbOfll 3 1(4' -trifluoromfethylo 5 biphenyl-2-CarbOlYl) -amino]I -phenyll-aCetOXY) -ethyl]1 -2phenyl-maloflic acid diethyl ester, 00 o ~biphenyl-2-carbOlYl) -amino] -phenyl)-aCetoxy) -ethyl] -2ci phenyl-mafliC acid diethyl. ester, 2-phenyl-2- (2414- -triiluororethYl-biPhnYl-2carbonyl) -amino] -ben zoyloxy} -ethyl]I -malonic acid'diethyl ester, 2-(2-{3-methyl-4-1 -trifluoromfethyl-biPhenYl> 2 carbonyl) -amino] -benzoyloxY}-ethYl) -2-phenyl-maloliC acid diethyl ester, 2-(2-{2-chi-oro-4-[ -trifluoroffethyl-biPheflyl- 2 carbonyl) -amino] -ben zoyioxy} -ethyl) 2 -phenyl-malolic acid diethyl. ester.

2-phenyl-2-( 2- -trifluoroinethYl-biPhelYl-2carbonyloxy)-befzlOXY]ethYl)hmalonic acid diethyl. ester, 2- (2-{3-ethoxyca-rbOlYl- 4 -trifluoromethYlbiphenyl-2-carbolYl) -amino]-phenyl)-acetoxrmethYl)VZ phenyl-malolic acid diethyl ester, 2- (3-(3-dimethylCarbamlOJ- 4 -trifluoroniethylbiphenyl-2-carbolyl) -amino]-.phenyl)-prOpiolloxymflthYl) 2-phenyl-malofliC acid diethyl ester, 2- (3 -benzyloxycarbolY-4- '-trifluot-omethyl bi phenyl-2-carbolYl) -amino] -phenyl)-acetOXYflethYl) -2phenyl-malolic acid diethyl ester.

carbonyl) -amino] -phenyl}-acetoxymethYl) -2-phenyl-naloflic en acid diethyl ester, 2-(2-{3-isoproposyCarbOl1-4-[ C4' -trifluoromethYlo 5 biphenyl-2-carbOlYl) -amino] -phenyl)-acttoxymethyl) -2phenyl-maloflic acid diethyl ester, 00 2-(2-{3-methoxycarbOlYl-4- -trifluoromethyo ~biphenyl-2-CarbOflyl) -amino] .phenyl)-acetoxYflethYl) -2- 0 phenyl-nalofliC acid diethyl ester, 2- (2-f 3-acetylaminO-4- -trifluoromethY1-biPhel- 2-carbonyl) -amino] -pheny11-acetoymfethYl) -2-phenyl-malolic acid diethyl ester, 2- (2-f 3-rnethoxycarbolyllfiflo- 4 -trifluoromethylbiphenyl-2-carbOlYl) -amino] -pheny1)-actOXymfethYl) -2phenyl-malOflic acid diethyl ester, 2-2{-4mty-hao--l--('tiloo inethyl-bipheflyl- 2-carbonyl) -amino) -phenyll -acetoxynethyl) 2-phenyl-ma-ofliC acid diethyl ester, 2-phenyl-2- (2-f 6- -trifluorornethY1-biPbenY1-2carbonyl) -amiLno] -biphenyl-3-yl) -acetoxymethyl) -malonic acid diethyl ester, 2- (2-f 3-forrnyl-4- -trifluoromfethyl-bipheflyl-2ca-rbony-) -amino] -phenyl)-acetOXylethYl) -2-phenyl-Inalonic acid diethyl ester, 2- (2-f 3-dimethylamiOmfethyl-4- -trifluorornethylbiphenyl-2-CarbolYl) -amino] -phenyl)-acetoxYmethyl) -2phenyl-malorlic acid diethyl ester, 2- (2-13- (methoxy-methylcarbaf l) -trifluoronethyl-biphenyl-2-carbOflYl) -amino] -phenyl)-acetoxymethyl) 2-phenyl-malolic acid diethyl ester, 2- (2-(3-isobutyryl-4- 1(4' -trifluoromethyl-biPhelyl- 2-carboflyl) -amino] -phenylJ-aCetOX-YmethYl) -2-phenyl-malolic acid diethyl ester, and o 2-(2-{3-(1-hydroxy-2-methyl-propy1- 4 4 trifluoromethYl4)iPhelyl-2-carbonYl) -amino] -phenyl} 00 acetoxymethy)-2-PhelYl-falonic acid diethyl ester; Ci (27) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of -trifluoromethyl-bipheyl-l2carbonYl) -amino] phenyll-acetic acid 2. 2-bis-ethylcarbamolY2-Pheflyl-ethyl ester, (3-ethyl-4- -trifluoromethYl-biPheyl-l2-carbonYl) amino] -phenyl)-acetic acid 2, 2-bis-ethylcarbaloyl-2phenyl-ethyl ester, -trifluoromethyl-biPhel-l2-carbolYl) -amino] phenyli-acetic acid 2-phenyl-2,2-biS-(2,2,2-trifluoroethylcarbamfoyl)-ethYl ester, '-trifluoromethYl-biPheyl-l2-carbonyl) -amino] phenyl}-acetic' acid 2, 2-bis-cyclohexylCarbamoyl- 2 phenyl-ethyl ester, -trifluoromfethYJ.TiPhnfl-lcarbonYl) -amino) phenyl)-acetic acid 2-phenyl- 2, 2 -bis -phenylcarbafl -ethyl ester, t(4' -trifluoromethYl-biPhenY1-2-carbonYl) -amino] phenyl)-acetic acid 2, 2-bis-isoproPYlcarb11oy1- 2 phienyl-ethYl ester, (biphenyl- 2-CarborlYl) -amino -phenyl) -acetic acid 2-phenyl-2, 2-bis-( 2,2, 2-trifluoro-ethylCarbamOYl) -ethyl ester, 2-phenyl-2-(2-(2-trifluorOmethYl- 4 A -trifluoroo ~5 methyl-bipheflYl-2-CarbOlYl) -amino] -phenyl)-aCetOXYifethYl) malonic acid diethyl ester, 00 ci -trifluoromethy1-biPhefl-2carbonYl) -amino] o phenylli-acetic acid 2, 2 -bis -methylcarb1foYl-2 -pheflyl-ethyl ci ester, -triiluoromethy1-biPhefYl-2CarbOnYl) -amino] phenyl)-acetiC acid 2, 2-bis-butylcarbamoyl-2-PhelYl-ethYl ester, (3-methyl-4- -trifluoromethY1-biPhelYl- 2 carbonyl) -amino] -phenylj-acetic acid 2, 2-bis-ethylcarbamoy1-2-phenyl-ethYJl ester, F trifluoromethy-biphelJ-2CarbOlYl) -amino] phenylli-acetic acid 3, 3-bis-ethy2lcarbamoyl-3-PheflYl-PrOPYlester, -trifluoromethyl-biPheflYl-2-CarbolYl) -amino] phenylil-aCetic acid 3-phenyl-3,3-bis-propyl- carbamnoylpropyl ester, 4- (biphenyl-2-carbOlyl) -amino] -phenyll-acetic* acid 2, 2-bis-ethylcarbIfoyl-2-PheflYl-ethYl ester, -trifluoromethyl-biphenfl-2-carbOflYl) -amino] phenyl)-acetic acid 2, 2-bis-isobutylcarbamoy-2-PhelYlethyl ester, -trifluoromethyl-biphenyl-2-carbolYl)-amino] phenyl)-acetic acid 2, 2-bis- (3-methyl-butylcarbamoyl) -2phenyl-ethyl ester, U 4 4 t-chloro-bipheny-2carbony)-amino>-phenyl)acetic acid 2,-i-tycraol2pey-ty ester, Mf 4 3 r4dichlorOphhflyl2.carbOflYl)am~ifl phenyll-aCetiC acid 2, 2-bis-ethyc8bWmolY2PhenYl-ethYl o 5 ester, {3-methyl-4- -trifluorometbyI-biPhel-l 2 c-icarbonyl) -amino] -phenyl)-acetic acid 2-phenyl- 2,*2-biso propylcarbamoyl-ethyl ester, Ci -trifluoromethy1-biPheylY2carbonY1)-aminol phenyl}-acetic acid 2, 2-bi-s- (2-methoxy-ethYIcSarbamOYl) 2-phenyl-ethy- ester, (3-isopropyl-4- -trifluorornethY1ThiPhelYl-2carbonyl) -amino] -phenyl-acetic acid 2 ,2-bis-ethylc8rbafolOY- 2-pheny)l-ethyl ester, {3-ethyl-4- -trifluoromethy1-biphenfl> 2 carbonyl) -amino] -phenyll-acetic acid 3,3-bis -ethylcarbamoyl-3-pheflYl-PrOPYl ester, (3-isobutyl-4-[(4' -trifluoroinethYl-biPhelYlcarbonyl)-a:lfl] -phenyl}-acetic acid 2,2-bis-ethylcarbamoyl-2-phelJ-thYl ester, {3-dirnethylcarbamfOYl- 4 -trifluorofethYlbiphenyl-2-CarbOlYl) -amino] -phenyl)-aCetic acid 2-phenyl- 2, 2-bis-propy1carbamfl-ethYl ester, (3-methylcarbafoyl- 4 -1(4 '-trifluorOmfethyl-biPhel1 2-carbony1) -amifo phenl)l-acetic acid 2,2-bisethylcarbamoyl-2 -phenyl-ethyl ester, {3-dimethylcarbamoyl- 4 -trifluoromethylbiphenyl-2-cabol)-amino] -phenyl)-Bcetic acid 3,3-bisethylcarbamoyl- 3-phenyl-propyl ester, o ~(3-benzylcarbafOyl- 4 -trifluorometbY1-biPhel- 2-carbonyl)-aminO1-phel)-aCetiC acid 2,2-bisethylcarbamOyl- 2-phenyl-ethyl ester., {3-dirnethylcarbam~oyl- 4 -trif luoromethylo 5 biphenyl-2-carbOlYl) -amino] -phenyl}-acetiC acid 4,4-bis- 00 ethylcarbamOyl- 4-phenyl-butyl ester, c-i (3-diethylcarbalOyl-4- -trifluoromethyl-biphelylo 2-carboflyl) -amino] -phenyl)-acetiC acid 2,2-bisci ethylcarbainoyl- 2-phenyl-ethyl ester, C 3-diisopropylcarbamfoYl-4- -trifluoromethylbipheny1-2-ca.rbofYl) -amino] -phenyll-acetic acid 2, 2-bisethylcarbaioyl-2-phelYl- ethyl ester, 3-A isopropyl-methylcarbamOyl- 4- '-trifluoro rnethyl-bipheflYl-2-Carbolyl) -amino] -phenyl)-acetiC acid 2, 2-bis-ethyCrbamfOyl-2phenyl-ethyl ester, (ethyl-methylcarbarloyl-4- -trifluoroinethylbiph(nyl- 2-carbolyl) -amino]I -phenyll -acetic acid 3,3-bisethylcarbamoyl-3 -phenyl-propyl ester, (piperidine-1-Carbolyl) -tritluorom~ethylbiphenyl-2-carbolYl) -amino] -phenyl)-acetiC acid 2 .2-bisethylcarbalnoyl- 2-phenyl-ethyl ester, (pyrrolidine-1-carbonyl) -trifluoromethylbiphenyl-2-carbOlYl)-ailo] -phenyl)-acetic acid 2 ,2-bisethylcarbamfoYl- 2-phenyl-ethyl ester, (zethyl-propylCarbafoyl) -trifluoromethyl- Sbiphenyl-2-carbolyl) -amino] -phenyl)-acetic acid 2,2-hisethylcarbamfoyl- 2-phenyl-ethyl ester, (methyl-propylcarbaloyl) -4-114' -trifluoromethylbiphenyl-2-CarbOYl)-ainl-phenyiji-acetic acid 3, 3-bisethylcarbamoyl-3-PheflYl-PrOPYl ester, {3-hydroxy-4- -trifluoromethY1-biPhelJ 2 carbonyl) -amino]-phenyl)-acetic acid 2 ,2-bisethylcarbalOyl-2-pheflYl-ethYl ester, {3-methoxy-4- -trifluoromethY1-biPhenfl-l> carbonyl) -anino]-phenyl)-acetic acid 2, 2-bisethylcarbarnOy1-2-pheDYJ.-ethYl ester, (3-methoxy-4- -trifluorornethy1-biPhefyl-l> carbony1)-amilO)-PheflYl)-aCetic acid 2-phenyl-2,2-bispropylcarbamnoyl-ethyl ester, {3-methoxy-4- -trifluoromethy1-biphelU 2 carbonyl) -amino] -phenyl)-acetic acid 3,3-bisethylcarbamoyl -3 -phenyl -propyl ester, (3-ethoxy-4- -trifluoromethy1-biPhefll 2 carbonyl) -amino] -phenyl)-acetic acid 212-biBethylcarbanOy1-2-phel-ethYJl ester, 3-ethoxy-4- -trifluoromnethY1-biPhefll 2 carbonyl) -amino] -phenylj'-acetic acid 3,3-bisethylcarbanoy--3 -phenyl-propyl ester, 3- isopropoxy- 4- -trifluoromethyl-biPhefl>2carbonyl) -amino] -pheniylil-acetic acid 2, 2-bisethylcarbamOyl-2 -pheflyl-ethyl ester, {3-isopropoxy-4-[ -trifluoromethy1-biPheflYl- 2 carbonyl) -amino] -phenyll-acetic acid 3, 3-bisethylcarbalOyl- 3-phenyl-propyl ester, 3-propoxy-4- -trifluoromethy1-biPhenyl-2carbonyl) -arinol-pheryll-acetic acid 2, 2-bisethylcarbafoyl-2-pheflLethYl ester, {3-benzyloxy-4- -trifluOrorflthYl-biPhenY> 2 carboflyl) -amino] -phenyl)-acetiC acid 2, 2-bisethylcarbafoyl> 2 -phenyl-ethyl ester, f3-dimethylamiflo- 4 -trifluoromethY1-biPhenYl- 2 o 5 carbonyl) -amino] -phenyl)-aCetic acid 2, 2-bisethylcarbafOYl2-PhenYl-ethYl ester, 00 c-I {3-piperidifl-l-Yl- 4 -trifluoromethYl-biPhefl- 2 o ~ca-rbonyl)-ainfO] -phenyl)-acetic acid 2, 2-bisethylcarbalDOyl2-PhenYl-ethYl ester, {3-pyrrolidif-1-Yl- 4 -trifluoromfethYl-biPhenYl 2 carbonyl) -amino] -phenyl)-aCetic acid 2, 2-bisethyicarbamfoyl phenyl -ethyl ester, trifluoroffethYlbiphenYl>>carbo~yl) -amino] benzoic acid 31 3-bis-ethYlcarbamOYl3-PhenYl-Propyl ester, 5- 2 -bis-ethy1Carb8ThOyl2PhenYl-ethoxcycarbonylmethyl) -trifluoromethYl-biPhenYl-2-carbonYl) axnino]-beflzOic acid benzyl ester, 2 -bis-ethylcarbamOYl2-PhellethoxcYcarbonYlmethyl) trif luoromethyl -biphernyl carbonyl) axnino]-beflZOiC acid, (2,2-i-tycramy -hnletoyabnl methyl) '-trifluoromethYl-biPhefyl-l-carbonY1)-amino] benzoic acid ethyl ester, and 2 -bis-ethylCarbamoyl2-phefl-ethoxycarbonYlmethyl) ((4'-tiloomty-ipey -cr y) amino]-beflZoic acid methyl ester; (28) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of 2-(2-{3-methy1-4-[(4'-trifluoromethyl-biphel- 2-carbonyl) -amino] -phenyl)-acetoxyrnethyl) -2-phenyl-malonic acid diethyl ester, o 2- [methyl- -trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl)-acetoxyinethyl) -2-phenyl-nialonic 00 ci acid diethyl- ester, o 2-phenyl-2-(2-(4-[(4'-trif1uoromfethyl-biphel- Ci 2-carbonyl) -amino] -phenyl}-acetoxymfethyl) -malonic acid diethyl ester, 2-phenyl-2- -trifluoromethyl-biphenyl- 2 -carbonyl) amino] -phenyl) -acetoxymethyl) -in lonic acid diisopropyl ester, 2-phenyl-2- -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -malonic acid dimethyl ester, 2-cyclopentyl-2- -trifluoromethyl-biphenyl- 2 -carbonyl) -amino] -phenyl) -acetoxymethyl) -malonic acid diethyl ester, 2-phenyl-2- '-trifluoroznethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -malonic acid dicyclohexyl ester, 2-benzyl-2- -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -ialonic acid diethyl ester, 2-methyl-4- '-trifluoromethyl-biphenyl- 2-carbonyl) -amino] -phenyl)-acetox-ymethyl) -2-phenyl-malonic acid diethyl ester, 2-cyclohexyl-2- -trifluoromethyl-biphenyl- 2-carbonyl) -amino] -pheny1)-aCetOXYfl1thYl) -malonic acid diethyl ester.

methy1-biPhel-2-CabOflYl) -amino] -pheny1)-8CtOXYflethYl) o 5 mnalonic acid diethyl- ester, 2-pyridin-2-Y-2-(21 4 4[( 4 '-trifluoromlethyl- 00 ci biphenyl-2-C5.rbOflYl) -amino] -pheny1)-aCetOXYmethYl) malonic o acid diethyl ester, 0 2-pyridin-3-y-2-{- 4 -trifluoroifethY1biphenyl-2-CarbOl) -amino] -pheny1}-aCtOXYmfethYl) malonic acid diethyl ester, 2-phenyl-2- (2-(3-trifluoroflethY1- 4 -trifluoromethyl-bipheflyl2-C8rbOlYl) -amino] -pheny1}-aCetoxylethYl) malonic acid diethyl ester, (41-methy1-biphefylY12Carbol)-amino]phenyJJ-aCetOXYmethYl) -2-phenyl-malolJC acid diethyl ester, 2-2(-('mtoyb hnl2croy)amino]phenyl)-acetOxYlfethYl) -2-phenyl-malonic acid diethyl ester, 2-phefl-2-( -trifluoromethYI-biPhelYl- 2 carbonyl) amino]I -phenyl) acetoxyrnethyl) -malonic acid diethyl ester, 24- tisopropyl-( 4 -trifJluoromflthy-biPhefyl 2 carbonyl) -amino] -pheny11-a.CetOXYTmethYl) -2-phenyl-falOfliC acid diethyl ester, 2- [cyc2.ohe'cyl-(4 trifluoromethy1-biPhelYl- 2 carbonyl) -amino] -pheny1)-acetOX-YflethYl) -2-phenyl-maloflic acid diethyl ester, 2-phenyl-2-(2-{ic[ (4'-trifluoromfethY1-biPheflYl- 2 carbonyl) -amino] -pheny1)-acetOXYmfethYl) -malonic acid 128 dipropyl ester, en carbonyl) -amino] -phenyl)-acetoxymethYl) -malonic acid diisobutyl ester, carbonyl) -amino] -phenyl}-acetoxymethYl) -2-phenyl-xnalofliC 00 acid diethyl ester, Ci carbonyl) -amino] -phenyl)-acetoxymfethYl) -2-phenyl-malonic acid diethyl ester, 2-(2-{3-isopropyl-4-(4' -trifluoromethy1-biphefl-2carbonyl) -amino] -phenyl}I-acetoxymfethYl) -2-phentrl-maloliC acid diethyl ester, 2-(2-{3-isobutyl-4-(4' -trifluoromethyl-bipheflyl-2carbonyl) -am-ino] -phenyl)-acetoxymethYl) -2-phenyl-malonic acid dielthyl ester, 2-(2-{3-chlOrO-4-(4' -trifluoromethy1-biPhefl- 2 carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyJ.-malonic acid diethyl ester, 2-(2-{3-brOmO-4-[ -trifluoromethyl-bipheflYl-2carbonyl) -amino] -phenyl I- acetoxymethyl) -2-phenyl-malOflic acid diethyl ester, 2- (2-{3-dimethylcarbamOyl--4- -trifluoromethylbiphenyl-2-CarbOlyl) -amino] -phenyll-acetoxylethyl) -2phenyl-malonic acid diethyl ester, 2-(2-{3-diethylcarbamyJ-4- -trifluoromethylbiphenyl carbonyl) -amino] -phenyl) -acetoxymethyl) -2 phenyl-malonic acid diethyl ester, 2- (2-{3-diisopropylcarbafoyl-4-[(4' -trifluoromethyo biphenyl-2-carboflyl) -amino] -phenyl)-acetoxymethYl) -2phenyl-maloflic acid diethyl ester, 2-(2-{3-(ethy IDethycrbBOYl)4[(4-trifluoromethyl-biphenyl-2-CarbOlYl) -amino] -phenyl}-acetOXyfethyl) -2 -phenyl-malonic acid diethyl ester, {0 3- (ethyj.-methylcarbamOyl) -4-L -trif2luoromethylci biphenyl-2-CarbOl) -amino] -phenyl)-acetic acid 2 .2-biso ethylcarbamoyl- 2-phenyl-ethyl ester, ci (3-(pyrrolidine--CarbOlYl)- 4 -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2 ,2-bisethylcarbanoyl -2 -phenyl-ethyl ester, 2-pheny1-2-(2-{3-(pyrrolidinfe--carbofylY)4-[( 4 trifluoromethyl-biphelYl-2-carbOl) -amino.] -phenyl)acetoxymethyl)-maloliC acid diethyl ester, 1s 2-hnl2(-3(ieidn--abnl--(' trifluoromethyl-biphel-2-CarbOlYl) -amiLno]--phenyllacetoxymethyl)-faloflic acid diethyl ester, 2- t2-(2-{3-dimethylcarbamfoyl-4- 1(4' -trifluoromethylbiphenyl-2-CarbOlYl) -amino] -phenyl)-acetosy) -ethyl]-2phenyl-malonic acid diethyl ester, 2-{3-dimethylcarbamoyl-4- -fluorobiphenyl-2-carbolYl) -amino] -phenyl)-acetoxyuethyl) -2phenyl-malonic acid diethyl ester, 2-(2-{4-[(4'bromo-bipheny1-2-Carbol)-amilo]1-3dimethylcarbamoyl-phelYl)-acetoxYllethYl) -2-phenyl-inalonic acid diethyl. ester, 2- (2-{3-diniethylcarbafoyl-4- -trifluoromethylbiphenyl-2-carbOrl) -amino] -phenyl)-acetoxyflethyl) -2phenyl-malolic acid dirnethyl ester, 2 -carbonyl) -amino] -phenyl) en acetoxymethy.)-maOloic acid diethyl ester, 00 2-cyclohex -hlrbiheyl-2-(2{3dmtycarb DY-- o ditrflrmetYl-PhelYl2-arton-Yme) -amn]-phenyl-mlon 0" actxynthl-mlflCacid diethyl ester, o ~dimethylcarbanoyl-PhelYll-acetox-yiethyl) -2 -phenyl-faJliC Ci acid diethyl ester, dimethylcarbamoyphel -aCetOXYflmethYl) -2-phenyl-malolic diethyl ester, dmethylcbamoeyl-pheflboYl-aetoymeyl) -peny-matli eylloi acid diethyl ester, 2- (2-{3-dimethyCarbamhOY2-4- [(4-methyl-4 -trifluoro- 20methy1-biphel1-2-CdrbofYl) -amino] -phenyl)-aCetOXYmfethYl) -2 -phenyl-malonic acid diethyl ester, 2-[3(2{3diethycarbamol-14-[45eh-trifluoroymelbyl- l-2ro-aifnl)-amino] -hey)-eOXyflltt-)- 2-phenyl-mal'nic acid diethyl ester, 252- [(2-{3-diethylcarbamOyl-4- trifloromthy tiloehlbiphenyl-2-carbonyl) -amino] -phenyl)-aeoy-ppl]actxty)2-phenyl-maloflic acid diethyl ester, (5-chloro-4'-trif1UOrOmfethY1-biPheflYl-2 carbonyl) -amino] -3-dimethyi-carbaxnOYl--phenYl)> acetoxymethy1I-2-pheny±Jnalonic acid diethyl ester, 2 2 3 dimethycabaOY4[ (6-methy1-4-trif luoroen methyl-biphelyl-2-CarbolYl) -amino] -phenyl)acetoxymethy1)-2-Phenflmalonic acid diethyl ester, o 5 2- 3-dimethylcarbamloYl- 4 U-trifluoromethylbiphenyl-2-carbOlYl) -amino] -pheny11-aCetOXYtfethYl) -2- 00 ci phenyl-malolic acid 2,2,2-trifluoroethyl ester, o 2-(2-{3-dimethy-carbamoyloY4(2fluoro- 4 0 ~trifluoromethYl-biPhelYl- 2 -carbonyl) -amino] -phenyl) acetoxymethyI)-2-PheflYl-malonic acid diethyl ester, 2- (2-{5-dimethy1CarbamolY2-fluoro- 4 trifluoromethy1-biphenflY1>carbonYl) -amino] -phenyl)acetoxymethy2)-b2Phtl-lmalonic acid diethyl ester, 2- (2-{3-bromo-5-dimfethY1carbamOYl- 4 '-fluoto-4' trifluoromethY1ThiPhefylY12-cabonYl) -amino] -phenyl)acetoxymethyly2-Phefllmalonic acid diethyl ester, 2- ?-{3.chloro-.5-dimfethYCarbamoYl- 4 trifluoromethy1-biPhefyl2CarbonY1)-amino] -phenyl)acetoxymethy1)-2-Phelmalo~nic acid diethyl ester.

2 -(2-3dimethycrbaoy4(3fluoro- 4 trifluoromethyl-biPhelYl- 2 -carbony-) -amino] -phenyl) acetoxymethyl-2-Phelmalonic acid diethyl ester, 2- (3 '-chloro-4'-trif luoromethiy1-biPhelYl- 2 .carbonyl) -amino1 dime thylc arb8hoy1-phel)acetoxymethyl-2-Phelyl-malonic acid diethyl ester, 2- (2-f3-dimethYlcarbamoyl- 4 -trifluoromethybiphenyl-2-Carbolyl) -amino] -phenyl)-aCetoxyflethYl) nitro-pyridin-2-Yl) -malonic acid diethyl es;ter, 2-5aioprdn2y)2(-3dmtycraol 4- -trifluoromethy1-biphel-2-CarbOflYl) -amino] phenyl-acetoxymflthYl)-malOlic acid diethyl ester, Mn 2- (2-{3-dimnethyC8rbamoflO2-4- '-trifluorometbybiphenyl-2-carbonyl) -amino] -phenyl)-acetoxymethYJ.V2 o 5 pyridin-2-yl-maloliC acid diethyl ester, 2-2(0hlr--ietycramy 00 trif luoromethy1-biPhefl2-Ca~boflYl) -amino]I -phenyl} o acetoxymethyl)-2-Phel-maOliC acid diethyl ester, 2-2(-rm--imtylabmyi-loo4 trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl} acetoxymethyl)-2-Phel-lalofliC acid diethyl ester, 2-{3-diinethylcarbamfoyl-4-[ -trifluorometh-ibiphenyl-2-cabOlyl) -amino] -phenyl}-acetoxyflethyl- 2 -0tolyl-malonic acid diethyl ester, 2-(2-{3-dimflthylcarbamOyl-4-[ -trifluoroinethylbiphenyl-2-carbolYl) -amino] -phenyl}-acetOXyflthY)-2 -intolyl-malonic acid diethyl. ester, 2- (2-{3-dinethylcrbaflJ-4- (4 -trifluoroinethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetoxyinethYl -ptolyl-malonic acid diethyl ester, 2-(2-chloro-pheny1)-2-(2-3-dimelthY1carbamoyl- 4 -trifluoromethyl-biPheflYl-2-CarbolYl) -amino] -phenyl)acetox-ymethyl-nalolic acid diethyl ester, 2-(3-chloro-pheny1)-2-(2-(3-diLmethycarbamoyl- 4 -trifluoromethY1-biPhenfl-2-CarbOflYl) -amino] -phenyllacetoxynethyl)-naloflic acid diethyl ester, 2-(4-chlorO-phelyl) -2-(2-{3-dimethylcarbaflOYl-4- -trifluoromethyl-biphelyl-2-CarbOl)-amino] -phenyl)acetoxyinethyl )-malonic acid diethyl. ester, o (2-{3-dtnethy1Carb8IflY 4 -trifJ-uoromethYlbiphenyl-2-carbOlYl)-amino] -pheny1)-aCetoSYiflthYl -2 mtyphenylifl ic acid diethyl ester, 2-(2-(3-dimethylCarbamolY4-[(4' -trifluorometllylo biphenyl-2-CarbOlYl) -amino] -pheny1)-acetoxymfethYl)H2- (2- 00 znmethoxy-phenlyl)-malOflic acid diethyl. ester, 2- (2-(3-dirnethy1CarbazmOYl- 4 -trifluorOmetbylo ~bipherxyl-2-carbolYl) -amino] -pheny1)-aCtOXYfl'ethYl (3ci rnethoxy-phenyl)-lalOfliC acid diethyl ester, 2- (2-{3[(4-dityc~bl- 4 ('-trifluoromethyl-bihnl2 biphenyl2-carboflyJ-} -amino] -pheyl-acetoymeh) h- 4 metoxymeh--phenyl-malonic acid diethyl ester, (5,4'lorbistr1UuOrflethY.-biPheYl- 2 carbonyl) -amino] r 3 dimethycarbmfl-Phefl)acetoxyniethyl)-2-PhenYi-malolic acid diethyl ester.

2 rfurmtybihnl2carbonyl) -amino] 3lietycr8IlY- heny acetoxymethyl)-2-PhelYl-malolic acid diethyl ester, 2-[2(2-3-dimethyaraTmOYl- 4 luor-4 20trifluoromethy1-biPhenY1-2-CarbonYl) -amino] -phenyl)acetoxymethyl-2-phel-alolic acid diethyl ester, 25[2-(2-(3-diethYcarbamoY-4-[(5-methy-4 trifluoromnethY1-biPhenfl-2-CarbonYl) -amino] -phenyl)acetoxymethyl2-Pheyl-falOflic acid diethyl ester, 2- (2-{3-dimethylCarbamhOYl- 4 -[E(5-isopropoxy-4' trifluoromethy1-biphefylY2-carbonYl) -amino] -phenyl)- 134 adetoxymethyl)-2-PhenYLiflalOnic acid diethyl. ester, en carbonyl) -amino] -3-dimethyCarbX1 Oy1-Phenfl>aCetOxY) ethyl)-2-phel-maloliC acid diethyl ester, methyl-biphel-2-CarbOlYl) -amino] -phenyl}-aceto xYlfethyl 00 2-phenyl-inalOflic acid diethyl ester, o 21-iehla~baol4(-ety-'tiloo methyl-biphelyl- 2-carbonyl) -amino] -phenyl} -acetoxytnethyl 2-phenyl-mJOliC acid diethyl ester.

dimethylcarbam~OYl-Phnfll-acetoxymethyl)>2 -phenyl-mnalonilc acid diethyl. ester, 2- (2-{3-dimethylcarbamlOYl-4- -methyl-biphelyl-2carbonyl) -amino] -pheny1)-acetOXYflethYl)h2-Phefl-mlOflic acid diethyl ester, 2-f 2- 13-diniethylcarbalOYl-4- (2-ethyl-4-trifluOrOmnethyl-belZOyafilO)-phenyl] -acetoxmethyl)2-Phlmalonic acid diethyl ester, 2-{3-dimethylcarbamOyl-4- -ethyl-biphel-2carbonyl) -amino] -pheny11-acetoxYmethY-2-PhflYl-maOliC acid diethyl. ester, 2-C 2-f3-dimethylcarbamOyl-4- -isopropenylzbiphenyl-2-carboflYl) -amino] -phenyl)-aCetOxyflethyl phenyl-malonic acid diethyl ester, 2-{3-diinethylCarbafoll-y4- 1(4' -isopropyl- biphenyl- 2-carbonyl) -amino] -phenyl) -acetoxyrnethy1)-2-Phelmaloflic acid diethyl ester, 2-f 3-dimethylcarbamoyl-4- -trifluoroniethylbiphenyl-2-carbOflyl) -amino] -phenyl)-acetOK-ymfethYl- 2 tbiophen-2-yl-malOliC acid diethyl ester, 2- (2-f 3-dimethylcarbamOy 1-4- -trifluorometby.biphenyl-2-carbOlyl) -amino] -phenyl)-acetOXYflethyl> 2 o thiophen-3-yl-nalOfliC acid diethyl ester, 2- (2-(4-dimethylcarbamOyl-5- -trifluoroniethyl- 00 ci biphenyl-2-carbOlYl) -amino] -pyridin-2-yll-aoetOxYflethYlho 2-phenyl-malOflic acid diethyl ester, Ci (2-f 3-dimethylcarbaloyl- 4 -trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyll-acetOXymflthYl-2 methyl-thiophel-2-Y1)-lalOfliC acid diethyl ester, 2- (2-f 3-di-methylCarbaflOyl-4- -trifluoromethylbiphenyl-2-carbOflyl) -amino] -phenyl}-aCetOXYmfethYlY-2- methyl-thiophen-2-y1) -malonic acid diethyl. ester, 2- (2-(3-dimethylcarbaflOYl-4- -trifluoromethylbiphenyl-2-carbOlyl) -amino] -phenyl)-acetOXymflthYl)-2 thiazol-2-yl-lalOfliC acid diethyl. ester, 2-2t-toy4[4-rfurmty-ihnl2 carbonyl) -amino] -pheny1)-acetoxymlthY1-2-Phel-ma1OliC acid diethyl ester, 2- (2-(3-methoxy-4- -trifluoromethyl-bipheflYl-2darbonyl) -amino] -pheny1)-acetoxymnethy1-2-Phel-maOliC acid diethyl ester, 2- (2-f 3-isopropoxy-4- -trifluoromethyl-biphenyl- 2-carbonyl) -amino] -pheny1)-acetoxynmethY1V-2-Phe1Yl-malOlic acid diethyl. ester, 2- (2-f 3-benzyloxy-4- -trifluoromethyl-biphelYl-2carbonyl) -amino] -phenyl)-acetoxyfethyl )-2-phenyl-malonic acid diethyl ester, 2- (2-{3-hydroxy-4- -trif luoromethyl-bipheflyl-2carbonyl) -amino] -pheny1} -acetOxymethy3)-2-Phefl-lm-lOfiC en acid diethyl ester, o 5 methyl-biphenyl-2-CarbOflYl) -amino) -phenyl}-acetoxyfethyl)malonic acid diethyl ester, 00 2-hnl2(-3proiin1y--('tiloo o' methyl-biphenyl-2-oarbOlYl)-amino) -phenyll-acetoxymethyl 0 malonic acid diethyl ester, 2- (2-(3-dimethylazino-4- -trifluoromethYlbiphenyl-2-carbolYl) -amino] -phenyl}-acetolymethYl phenyl-malonic acid diethyl ester, 2- (2-{3-morpholin-4-yl-4- -trifluoromethylbiphenyl-2-carbOlYl) -amino] -phenyl)-acetoxymethYl phenyl-inalonic acid diethyl ester, 2- (2-{3-diethylanfO-4-[114' -trifluoromethylbiphenyl-2-carbOlyl) -amino] -pheryl)-acetoxymethYl)-2 phenyl-inalonic acid diethyl ester, 2-C 2-{2-chloro-4- -trifluoromethyl-biphelYl-2carbonyl) -amiLno] -benzoyloxy)~-ethyl) -2-phenyl-malonic acid diethyl ester, 2-C 2-{3-ethoxycarbOflyl-4- -trifluoromethylbiphenyl-2-carbonyl) -amino] -phenyl}-acetoxymfethYl) -2phenyl-malonic acid diethyl ester, 2- (3-{3-dimethylcarbamoyl-4- -trifluoromethylbi-phenyl-2-carbOl) -amino) -phenyllj-propiolyloxymfethYl) -2-phenyl-malolic acid diethyl ester, 2-{3-benzyloxycarbOflyl-4- -trifluoromethylbiphenyl-2-carbony-) -amino] -phenyl)-acetoxymethyl) -2p heny-ma1Oli~C acid diethyl- ester, 2-(2-(3-carbOXY-44 4 '-trif1UOromethyl-biphenYl> 2 en carbonyl) -amino) I phenyJl)-aCetOXYflethYl) -2-phel-fai-liC acid diethyl ester, o 5 2 -(2-{3-isoprOpOXycabonY1' 4 -((4'-trifluorofethYlbiphenyl-2-CarbOlYl) -amino] -pheny1)-aCetOXYmfethYl) -2- 00 ci phenyl-malolic acid diethyl ester 1 o 2- (2-{3-methoxyCdrbOlYl- 4 -trif)luoromethY1- 0biphenyl -2-C8.rbOfYl) -amino] -pheny1}-acetOXYmflthYl) -2phenyl-malOflic acid diethyl ester, 2- (2-{3-acety-miflo- 4 -trifluorOmethYI-biPhenYl- 2-carbony))-amino] -pheny11-actOXYmfethYl) -2-pheny-fa1OfliC acid diethyl ester, 2- 2-t3methoxYCarbolamino- 4 1(4' -trif luoroilethylbiphenyl-2-carbOlYl) -amiLno] -pheny11-acetOX-YmflthYl) -2phenyl-maloflic acid diethyl ester, 2-2(-4mty-hao--l--('tiloo methy1-biphenfl-2-carbonYl) -amino] -pheny1-.cetOXYfflthYl) -2-pheny1-ma1oliC acid diethyl- ester., 2-phenyl-2- -trifluoromethy1-biphefyl-l> carbonyl) -amino] ihny--l-aeo-yehl-malonic acid diethyl ester, 2- (2-{3-formyl- -trifluoromethy1-biphenyl- 2 carbony-) -amino] -pheny1}-acetOXYflethYl) -2-pheflyl-maloflic acid diethyl ester, 2- (2-{3-dimethYailOmfethYl- 4 -trifluoromethylbiphenyl-2-OarbOlyl) -amino1-pheny1>-actOXYmIethYl) -2phenyl-naloflic acid diethyl ester, 2- (methoxy-flethylcarbamnOYl) -4-EI(4 -trifluoro- Inethyl-biphenyl-2-CarbOlYl) -amino] -phen'yl}-acetOXymnethY.) 2-phenyl-maloflic acid diethyl ester, Mn 2-(2-(3-isobUtyryl-4-f (4'-trifluorofetbyl-biPheflYl-2carbonyl) -amino] -phenyl)I-acetoxymethyl) phenyl-malolic o 5 acid diethyl ester, and 2(2-f{3-(1-hy6roxy-2-methyl-propyl)- 4 4 00 trifluoromethyl-biphelYl-2-CarbOlYl) -amino] -phenyl}o acetoxymethy-)-2-PhelYl-faloniC acid diethyl ester; (29) The ester compound or a prodrug thereof or a pharmaceutically acceptable salt of either according to the above which is'selected from the group consisting of 4' -trifluoromethyl-biphernyl-2-carboxylic acid 4-[2phenyl-2, 2-bis- 2-trifluoro-ethylcarbafoyl) ethoxycarbonylsnethyl] -phenyl ester, biphenyl-2-carboxylic, acid 4- [2-phenyl-2 ,2-bis- 2-trifluoro-ethylCarbafoyl) -ethoxycarbonylethyl

I-

phenyl ester, 4' -triiluoromethyl-bipheflYl-2-carbOxWlic acid 4- (2,2lis -ethylcarbainoyl- 2-phenyl-ethoycarbonYJ-llethYl) -phienyl ester, 4' -trifluoromethy-biphelYl-2-carbo2C~liC acid 4- (2,2bis -ethylcarbamoyl- 2-phenyl-ethoxycarboflylmfethyl) -2chioro-pheflyl ester, 4. -trifluoromethy1-bipheflyl-2-carboxylic acid 4- (3,3bis-ethylcarbamoyl-3-phefl-lprOPOXYcarbonYlmethYl) -2chioro-pheflyl ester, 4' -trifluoromethyl-biphenyl-2-carboxyliC acid 4- (3,3bis -ethylcarbamoyl- 3-phenyl-propoxycarbOlYl) -phenyl ester, and 4' -trifluoromethyl-biphefyll2-carboxylic acid 4- (3,3- Mn bis-ethylcarbamoyl-3-phel]ProcycarbonYl) 6-dichj-oro-p henyl ester; The ester compound or a prodrug thereof, or a 00 pharmaceutically acceptable salt of either according to the o above which is selected from the group consisting of carbonyloxy) -phenyl] -acetoxymethyl}-malolic acid diethyl ester, 2- [3-dimethylcarbaloyl- 4 -trifluoroulethylbiphenyl-2-Carbolloxy)-phenyll -acetoxymethylj'-2-Phefl malonic acid diethyl ester, 2-{2-[3-methOxy-4-(4' -trifluoroinethy1-biPhefYl-2 carbonyloxy) -phenyl] -acetoxymethyl}-2-Phelyl -malonic acid diethyl ester, and 4- -trifluoromethyl-biPhelYl-2-crbonYl) -amino] benzoic acid 3-[2-(2,2,2-trifluoro-ethYlcarbamoyl)naphthalen-1-Y1II-Propyl ester; (31) The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to the above which is selected from the group consisting of 2-{3-dimethylcarbaIUoyl-4 -trifluoromethylbiphenyl-2-CarboriYl) -amino] -phenyll-acetoxylnethyl) -2isopropyl-malo'ic acid diethyl ester, 2-e-uy--(-3dmtylabmy trifluoromethyl-biPhefl-l-carbonYl) -amino] -phenyl)- U acetoxymethyl)-2-mlOliC acid diethyl ester, 2- (2-{3-dimethylcarbanmoYl-4- -trifluoromfetbylen bipheryl- 2-carbonyl) -amino] -phenyl) -acetoxymethyl) -2isobutyl-maloflic acid diethyl ester, o 5 2- (2-(3-dimethylCarb1fOYl- 4 -trifluoromethylbiphenyl-2-CarbOlYl) -amino] -pheryl}-aCetOXymfethYl) -2- 00 propyl-ialoflic acid diethyl ester, Vo 2- dimethylcarbaflOYl- 4 -trifluoromfethyl- 0 biphenyl-2-Carbolyl) -amino] -phenyl}I-aCetOXYmfethYl) 2 -ethyl malonic. acid diethyl ester, 2-buty1-2-(2-{3-dimethylcarbamoyl- 4 4 trifluoronethyl-biphel-2-carbonyl) -amino] -phenyl} acetoxymethyl)- malonic acid diethyl ester, 2-allyl-2- (2-{3-dimethylCarbamfoYl- 4 trifluoromethYl-biPheflYl-2-CarbonYl) -amino] -phenyl}acetoxymethyl)-malOlic acid diethyl ester, 2-C 2-{3-dimethylcarbamlOyl- 4 '-tritluoroniethylbiphenyl-2-carbofl)amfino>phenyl)acetocy) 2 2 bis ethoxycarboflyl-ProPiOfliC acid ethyl ester, and 2-C 2-{3-dimethylCarbamOYl- 4 -trifluoromethylbiphenyl-2-carbolYl) -amino] -phenyl}-aCetoxyflethyl) (1methyl-butyl)-falofliC 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 to (31) and a pharmaceutically acceptable carrier; (33) An MTP (microsomal triglyceride transfer protein) c inhibitor, which comprises the ester compound or a prodrug

O

Sthereof, or a pharmaceutically acceptable salt of either Cn according to any of the above to (31) as an active ingredient; ci O 5 (34) An agent for the treatment or prophylaxis of hyperlipidemia, 0> which comprises the ester compound or a prodrug thereof, or a 00 pharmaceutically acceptable salt of either according to any of Sthe above to (31) as an active ingredient; ci (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 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 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 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 to (31) as an active ingredient; (39) An agent for the treatment or prophylaxis of hypertension, en which comprises the ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any of the above to (31) as an active ingredient; 00 An agent f or the treatment or prophylaxis of hyperli-pidemia, V) arteriosclerosis, coronary artery diseases, obesity, diabetes ci 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 inhibi-tor does not substantially inhibit MTP in the liver but substantially inhibits only MTP in the small intestine; (42) The agent f or the treatment or prophylaxis according to the above 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 (4 2) 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; ci S(44) The agent for the treatment or prophylaxis according to cn the above (40) to wherein the MTP inhibitor is a compound having at least one ester bond; o Oh (45) The agent for the treatment or prophylaxis according to 00 the above wherein after the compound having at least one o ester bond exerts MTP inhibitory activity, the ester moiety of 0 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 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 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 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 wherein .the C remaining compound in the liver is metabolized to the state o 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 to wherein iV the compound has at least one ester bond; 00 (51) The method according to the above wherein after the o 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; (52) The-method according'to the above to wherein the compound -is the ester compound or a prodrug thereof, or a pharmaceutically .acceptable salt of either mentioned in any of the above to (31); The agent for the treatment or prophylaxis according, to the above (40) to 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 wherein other antihyperlipidemic drug is a statin-type drug; The agent for the treatment or prophylaxis according to the above wherein the statin-type drug is one or more drug(s) selected from the group consisting of- lovastatin, simvastatin, pravastatin,' fluvastatin, atorvastatin and cerivastatin: ci (56) The agent for the treatment or prophylaxis according to O 5 the above (40) to wherein the agent is an agent for the 0\ treatment or prophylaxis of obesity which is used in combination 00 with other anti-obesity drug(s); In (57) The agent for the treatment or prophylaxis according to the above wherein other anti-obesity drug is mazindol or/and orlistat; (58) The agent for the treatment or prophylaxis according to the above (40) to 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 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 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, C- metformin hydrochloride, buformin hydrochloride. boglibose, Sacarbose and pioglitazone hydrochloride; Ci (61) The agent for the treatment or prophylaxis according to O 5 the above (40) to wherein the agent is an agent for the 01 treatment or prophylaxis of hypertension which is used in 00 Scombination with other anti-hypertension drug(s); (62) The agent for the treatment or prophylaxis according to the above wherein other anti-hypertension drug is one or more drug(s) selected from the group consisting of loop diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, p-blockers, a,p-blockers and a-blockers; (63) The agent for the treatment or prophylaxis according to the above 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, C efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, n propranolol hydrochloride delayed release, pindolol, pindolol delayed release, indenolol hydrochloride, carteolol O 5 hydrochloride, carteolol hydrochloride delayed release, 0\ bunitrolol hydrochloride. bunitrolol hydrochloride delayed 00 release, atenolol, asebutolol hydrochloride, metoprolol Startrate, metoprolol tartrate delayed release, nipradilol, C 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; (64) Use of the agent for the treatment or prophylaxis according to the above (40) to and other antihyperlipidemic drug(s) for the treatment or prophylaxis of hyperlipidemia; The use according to the above wherein other antihyperlipidemic drug is a statin-type drug; (66) The use according to the above wherein the statin-type drug is one or more drug(s) selected from the group consisting of lovastatin. simvastatin, pravastatin.

fluvastatin, atorvastatin and cerivastatin; o (67) Use of the agent for the treatment or prophylaxis according Qto the above (40) to (46) and other anti-obesity drug(s) for Sthe treatment or prophylaxis of obesity; ci O 5 (68) The use according to the above wherein other a 0 anti-obesity drug is mazindol or/and orlistat; ci o Use of the agent for the treatment or prophylaxis according Ci to the above (40) to (46) and other anti-diabetic drug(s) for the treatment or prophylaxis of diabetes; The use according to the above 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 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; (72) Use of the agent for the treatment or prophylaxis according to the above (40) to (46) and other anti-hypertension drug(s) for the treatment or prophylaxis of hypertension; o (73) The use according to the above wherein other m anti-hypertension drug is one or more drug(s) selected from the group consisting of loop diuretics, angiotension converting O 5 enzyme inhibitors, angiotension II receptor antagonists.

00 calcium antagonists, beta-blockers, alpha/beta blockers and 00 alpha blockers; Ci (74) The use according to the above 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 ci tartrate delayed release, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fumarate, c betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride. labetalol hydrochloride, O 5 arotinolol hydrochloride, amosulalol hydrochloride. prazosin o0 hydrochloride, terazosin hydrochloride, doxazosin mesylate, 00 N bunazocin hydrochloride, bunazocin hydrochloride delayed o release, urapidil and phentolamine mesylate; 0 (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 to a pharmaceutically acceptable, appropriate amount of ethanol and propylene glycol fatty acid ester; (76) The pharmaceutical composition according to the above which comprises 25.to 35% by weight of ethanol and 65 to 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) 151 ,l R2 0 (CH2,)I RSo N A N (100)

SRH

00 R' I wherein 0 R' is hydrogen, .Ci-C 6 alkyl, halogen, halo CI-C 6 alkyl or

C

1

-C

6 alkoxy;

R

2 is hydrogen,' C 1

-C

6 alkyl, halogen, halo C 1 -C alkyl or C2-C 6 alkenyl;

R

3 .is -CON(R1la)(R 12a 'wherein R 1a 1 l and R 12L are each independently hydrogen, C 1

-C

6 alkyl, optionally substituted

C

6

-C

4 aryl, optionally substituted C 7 -Ce 6 aralkyl, C 1 -C alkoxTy, or R 11 and R 12a may be taken together with the nitrogen to which .they are attached to form.

(in which p is an integer of 0 to 2); R 'is hydrogen, halogen, CI-C 6 alkyl or halo Ci-C 6 a2ky:l

R

50 is hydrogen,. Ci-C alkyl, optionally substituted C 6

-C

14 aryl or optionally substituted C7-C 1 6 aralkyl; and la is an integer of 1 to 3, or a prodrug thereof, or a pharmaceutically acceptable salt of either; The biphenyl compound according to the above (79), 152 0 0 CA wherein

R

1 is hydrogen, n

R

2 is halo CI-C 6 alkyl, c" R3 is -CON RIb

(R

1 2 b 1 wherein R 1 3 .and R 1 2 b are each o 5 independently hydrogen or C-C6 alkyl, or Rlb and R 12 b may be taken O! together with the nitrogen to which they are .attached to form 00 o -N -p

(NN

ci (in which p is an integer of 0 to 2),

R

4 is hydrogen, and

R

s is hydrogen or. Ci-C 6 alkyI, or a prodrug thereof, ora pharmaceutically acceptable salt of either.; (81) The use of the ester compound:or a.prodrug thereof, or a pharmaceutically acceptable salt of either according to any of the above. to (31) for the preparation of a medicament for the treatment or prophylaxis of hyperlipidemia; (82) The use of the ester compound or a prodrug thereof, or a pharmaceutically acceptable -salt of either according to any of the above to (31) for the preparation of a medicament for the treatment or prophylaxis of arteriosclerosis; (83) The use of the ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any of the above to (31) for the preparation of a medicanent for the treatment br prophylaxis of coronary artery diseases; 152a (84) The use of the ester compound or a prodrug thereof, or-a pharmaceutically acceptable salt of either according to any of the above to (31) for the preparation of a medicament for the treatment or prophylaxis of obesity; 'The use of the ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any of the above to (31) for the.preparation of a medicament for the treatment or prophylaxis of diabetes; (86) The use of the ester compound.or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any of the above to (31) for,the preparation of a medicament for the'treatment or prophylaxis .of hypertension; (87) The use of MTP inhibitor which selectively inhibits

MTP

in the small intestine for the preparation of a medicament for the treatment or prophylaxis of hyperlipidemia, arteriosclerosis, coronary artery diseases, obesity, diabetes or hypertension; (88) The use according to the above wherein theMTP inhibitor does not substantially inhibit MTP in the liver but substantially inhibits only MTP in the small intestine; (89) The use according to the above 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; 152b The use according to the above 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; (91) The use according to the-above (87) to wherein the MTP inhibitor is a compound having at least one ester bond;.

(92) The use according to the above 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; and (93) The use-according to the above (87) to 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 to (31) The definitions of each substituent used in'the present invention are as follows.

"CI-C

6 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 R 1

R

2

R

2 and R 2 'include methyl, -ethyl or isopropyl; preferable examples for R 3 and R 4 include methyl, ethyl, propyl; isopropyl, butyl or isobutyl; a preferable example for R 5

R

6 and R' includes methyl; preferable examples for R 8 and R 9 include methyl or ethyl; preferable examples for R 10 include methyl, C ethyl or isopropyl; preferable examples for R 11 and R 1 2 include methyl, ethyl, propyl or isopropyl; preferable examples for R 13 cn and R 14 include methyl or ethyl; a preferable example for R 1 includes isopropyl; preferable examples for R 16 and R 1 7 include O 5 methyl or ethyl; preferable examples for R 18 and R 19 include C0 methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, 00 tert-butyl, pentyl or isopentyl, more preferably ethyl; preferable examples for R 20 include methyl, ethyl, propyl, 0 isopropyl or isobutyl, more preferably ethyl: a preferable example for R 21 and R 22 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

C

1

-C

6 alkyl" include halogen, carboxyl, hydroxy, amino, nitro, cyano, Ci-C 6 alkoxy, C7-C 1 6 aralkyloxy, C 2 -C7 alkoxycarbonyl,

C

6

-C

1 4 aryl, CI-C 6 alkylthio, CI-C 6 alkylsulfinyl, Ci-Cs alkylsulfonyl, CI-Cs alkylamino, acylamino and the like, among which hydroxy is preferable. The number of the substituents is 1 to 5, preferably 1 to 3.

"C

3

-C

7 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

R

1 and R 2 includes cyclohexyl; a preferable example for R 10 includes cyclohexyl; a preferable example for R 18 and R 19 includes cyclohexyl; a preferable example for R 20 includes .154 0 0

C

N cyclohexyl; and preferable examples for ring C include cyclopentyl or cyclohexyl. It is also preferable that R 8 and

SR

9 are taken together to form cyclopentyl or cyclohexyl.

"Cl-C 6 alkoxy" refers to a straight- or branched-chain O 5 alkoxy group having 1 to 6 carbon atom(s), and its example Ch includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, 00 tert-butoxy, pentyloxy, tert-pentyloxy or hexyloxy, etc., Spreferably an alkoxy having 1 to 4 carbon atom(s), such as 0 methoxy, ethoxy, isopropoxy, butoxy or tert-butoxy, and more preferably methoxy or ethoxy. Preferable examples for R. R 2

R

2 and R 2 include methoxy, isopropoxy or butoxy; preferable examples for R 3 and R 4 include methoxy, ethoxy, propoxy or isopropoxy; preferable examples for R 5

R

6 and R 7 include methoxy or ethoxy; a preferable example for R" and R 12 includes methoxy; and preferable examples for R' s include methoxy, ethoxy, propoxy or isopropoxy.

"Halogen" refers to chlorine, bromine, fluorine or the like. Preferable examples for R 1 include fluorine or chlorine; preferable examples for R 2 and R 2 include fluorine, chlorine or bromine; preferable examples for R 3 and R 4 include chlorine or bromine; and preferable examples for R 5

R

6 and R 7 include fluorine or chlorine.

"Halo Ci-C 6 alkyl" refers to said CI-C 6 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

c9 preferable 'example for

'R

2 R and R" includes U f R includes trifluoromethyl; a preferable example for R and includes trifluoromethyl; a preferable example for R 5

R

6 and R' includes trifluoromethyl; preferable examples for R' 6 and R 1 include o 5 trifluoromethyl or trifluoroethyl; and preferable examples for

R

1 and R19 include trifluoromethyl or trifluoroethyl.

00 "Halo C 1 -Cs alkyloxy" refers to, for example, 0 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 R 2

R

2 and R 2 includes trifluoromethylory.

C

2

-C

12 alkoxyalkyl" refers to an alkoxyalkyl of which alkoxy moiety has the same meaning as said alkoxy and alkyl moisty 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.

"C

2 alkylcarbonyl" refers to acetyl, -propionyl, butyryl or pivaloyl, etc., and a preferable example for R 21 and R22 includes acetyl.

"C

1 alkylsulfonyl" refers to methanesulfonyl, ethanesulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl or hexylsulfonyl, etc., and a preferable example for R 21 and R 22 includes methylsulf onyl.

"C

2 -C7 alkoxycarbonyl" refers to an alkoxycarbonyl of c which alkyl moiety has 1 to 6 carbon atom(s) such as methoxycarbonyl, ethoxycarbonyl. propoxycarbonyl, M isopropoxycarbonyl. butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, S 5 tert-pentyloxycarbonyl or hexyloxycarbonyl etc. Preferable examples thereof include methoxycarbonyl, ethoxycarbonyl,.

00 propoxycarbonyl or butoxycarbonyl. A preferable example for V0

R

2 includes butoxycarbonyl; a preferable example for R 5 R' and R includes methoxycarbonyl; a preferable example for R and R includes methoxycarbonyl; and a preferable example for and

R

1 4 includes methoxycarbol; and a preferable example for D includes ethoxycarbonyl.

"C

1

-C

6 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 R 2 and

R

2 includes acetyl: a preferable example for R 3 includes formyl; a preferable example for R5, R 6 and R' includes acetyl; a preferable example for R1 3 and R1' includes acetyl; and a preferable example for R 2 and R 22 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, hexane-1,6-diyl, 1,1-dimethylethane-1,2-diyl, 1,1-diethylethane-1,2-diyl, 2,2-dimethylethane-1,2-diyl, 2,2-diethylethane-1,2-diyl, 1,1-dimethylpropane-1,3-diyl 1,1-diethylpropane-1,3l. -diyl 2,2-dimethylpropane-1,3-diyl, 2,2-diethylpropane-1,3-diyl, 3,3-dimethylpropane -1,3-diyl or 3,3-diethylpropane-1, 3-diyl, etc. Preferable examples for Alk' and Alk 2 include methylene, 0 0 U ethane-1,2-diyl, ethane-1,1-diyl, propane-1,3-diyl, etc.

"Alkenediyl" has preferably 2 to 6 carbon atom(s), and Mn its example includes ethylene-1,2-diyl, 1-propene-1,3-diyl, 2-propene-1,3-diyl, 1-butene-1,4-diyl, 2-butene-1,4-diyl, o 5 3-butene-1,4-diylor 1,3-butadiene-1,4-diyl, etc. Preferable examples for AlkI and Alk 2 include ethylene-1,2-diyl, 00 1-propene-1.3-diyl, 2-propene-1,3-diyl, etc.

o"C 6 -C14 aryl" refers to phenyl, naphthyl or biphenyl, etc., preferably phenyl.

In the "optionally substituted

C

6

-C

4 aryl", the substituent(s) is/are not particularly limited, and maybe 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 Cj-C6 alkyl methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, etc.), hydroxy,

C

1

-C

6 alkoxy (e.g.

methoxy, ethoxy, propoxy, butoxy, etc.), halogen fluorine, chlorine, bromine, etc.), nitro, cyano, C,-C 6 acyl formyl, acetyl, propionyl, etc.), C 1

-C

6 acyloxy formyloxy, acetoxy, propionyloxy, etc.), mercapto, C-C6 alkylthio (e.g.

methylthio, ethylthio, propylthio. butyithio, isobutylthio, etc.), amino, C,-C 6 alkylamino methylamino, ethylamino, propylamino, butylamino, etc.), di(C,-C 6 alkyl)amino (e.g.

dimethylamino, diethylamino. dipropylamino, dibutylamino, etc.), carboxyl, C2-C, alkoxycarbonyl methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), amido, trifluoromethyl, C-Ce alkylsulfonyl(e.g. methylsulfonyl, ethylsulfonyl, etc.), aminosulfonyl,

C

3 -C cycloalkyl (e.g.

Ccyclopentyl, cyclohexyl, etc.), phenyl, acylamido (e.g.

Sacetamido, propionylamido, etc.) and the like, among which en hydroxy, Ci-Csalkyl, Ci-C 6 alkoxy, mercapto, Ci-C 6 alkylthio, halogen, trifluoromethyl,

C

1 -Cs acyl, C2-C7 alkoxycarbonyl and o 5 acylamido are preferable.

CA A preferable example for R 1 and R 2 includes phenyl which 00 may be substituted with halo Ci-C 6 alkyl trifluoromethyl, Setc.),

C

1

-C

6 alkyl methyl, ethyl, etc.), halogen (e.g.

^c fluorine, chlorine, bromine, etc.), C 1

-C

6 alkoxy methoxy, etc.), Ci-C 6 acyl acetyl, etc.), C 2

-C

6 alkenyl (e.g.isopropenyl, etc.) or cyano; a preferable example for R 5

R

6 and R 7 includes phenyl which may be substituted with halo

C

1

-C

6 alkyl trifluoromethyl, etc.), C 1 -C6 alkyl (e.g.

methyl, etc.), halogen chlorine, etc.) or CI-C6 alkoxy (e.g.

methoxy, etc.); a preferable example for R 8 and R 9 includes phenyl; a preferable example for R" and R 1 2 includes phenyl; a preferable example for R 18 and R 19 includes phenyl; a preferable example for R 43 includes biphenyl; a preferable example for ring A includes phenyl; and preferable examples for ring C include phenyl or naphthyl.

"C7-C 1 6 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 R 1 and R 2 includes benzyl; a preferable example for R 11 and R 1 2 includes benzyl; and a preferable example for ring C includes benzyl.

C

N

"C

6

-C

14 aryloxy" refers to phenoxy, naphthyloxy, etc.

S(where the phenyl group or naphthyl group may be substituted M with 1 to 3 substituent(s) mentioned in the above description of aryl), preferably phenoxy. A preferable example for R 1 and O 5 R 2 includes phenoxy, and a preferable example for R i 5 includes O\ phenoxy.

00

"C

7 -Ci6 aralkyloxy" refers to an arylalkoxy of which alkoxy VI moiety has 1 to 4 carbon atom(s) (where the aryl group may be 0 substituted with 1 to 3 substituent(s) mentioned in the above description of aryl), and example thereof includes benzyloxy.

phenethyloxy. phenylpropyloxy, phenylbutyloxy. etc., preferably benzyloxy. A preferable example for R 1 and R 2 includes benzyloxy; a preferable example for R 3 includes benzyloxy; and a preferable example for R 15 includes benzyloxy.

"C7-C, 5 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 R 1 and

R

2 includes benzoyl.

"C

7 -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.

"C

8 -Ci 6 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 benzycarbOflylamiO.

"heterocycle" refers to a 5 to 6 -membered heteroaromatic Mn ring, a 5- to 6-inembered 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 00 heterocyclic ring In which said heterocycle and benzene ring o are fused. Specifically, its example includes thiophefl-2-yl, 0thiophen-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 2 4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, pyrimidin-2-yl. pyri-midin-4-yl, pyrixnidiLn-5-yl1 pyridin-2-y1 3 pyridin-3-yl. pyridtn-4-yl, pyrrolidin-2-Yl1 pyrrolidin- 3 -yl 1 benzothiophen-2-Yl, benzothiophefl-3-Yl, benzofuran-2-yl, benzofural-3-yl, indol-2-yl, indol-3-yl, benzimidazol-2-Yl, benzimidazOl-2-yl, benzothiazol- 2 benzoxazol- 2 -yl. quinolin-2-yl, quinolin- 3 -Yl, quinolin-4-yl. isoquinolin-1-yl, isoquinolin- 3 -Yl, isoguinolil- 4 1,3, 4-thiadiazol-2-yl, morpholin-4-Yl. etc,.

A pref erable example f or Rt' and It 2 includes thiophen-3-yl; preferable examples for ring A include thiazol-5-Yl, pyridin-3-yl or pyrrolidin-2-yl; a preferable example for R 3 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 (N heterocycle", the same substituents as those mentioned in the above description of aryl may be exemplified. The number of Msubstituents is not particularly limited so long as they are chemically acceptable, while the number is preferably around 1 to 3.

O "C 2

-C

6 alkenyl" refers to a straight- or branched-chain 00 Salkenyl group having 2 to 6 carbon atoms, and its example ci V) includes vinyl, n-propenyl, isopropenyl, n-butenyl, Sisobutenyl, sec-butenyl, tert-butenyl, n-pentenyl, isopentenyl, neopentenyl, 1-methylpropenyl, n-hexenyl, isohexenyl, 1,1-dimethylbutenyl, 2,2-dimethylbutenyl, 3,3'-dimethylbutenyl, 3,3-dimethylpropenyl, 2-ethylbutenyl, etc. A preferable example for R 2 and R 2 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-C 1

-C

6 alkyl, -C0 2

-C

1

-C

6 alkyl,

-CONH-C

1

-C

6 alkyl, -CO-C--C 6 alkenyl, -C0 2

-C

2

-C

6 alkenyl,

-CONH-C

2

-C

6 alkenyl, -CO-C 6

-C

14 aryl, -C0 2

-C

6

-C

14 aryl,

-CONH-C

6

-C

14 aryl, -CO-heterocycle, -CO 2 -heterocycle, -CONH-heterocycle, etc. (wherein any of said CI-C 6 alkyl, C 2

-C

6 alkenyl, C 6

-C

14 aryl and heterocycle may be substituted with halogen, Ci-C 6 alkyl, hydroxy, Ci-C6 alkoxy, carboxyl, amino, amino acid residue, -P0 3

H

2 -S03H, -CO-polyethyleneglycol residue, -C0 2 -polyethyleneglycol residue.

-CO-polyethyleneglycol monoalkyl ether residue or S-COz-polyethyleneglycol monoalkyl ether residue) is attached n to the hydroxy group of the compound.

Also, there may be exemplified a derivative in which a 0 5 substituent such as -CO-CI-C6 alkyl, -C0 2

-CI-C

6 alkyl, -CO-C2-C 6 o\ alkenyl, -CO2-C 2

-C

6 alkenyl, -C0 2

-C

6

-C

1 4 aryl, -CO-C 6 -C14 aryl, 00 -CO-heterocycle,

-CO

2 -heterocycle, etc. (wherein any of said SCi-C 6 alkyl, C 2

-C

6 alkenyl,

C

6

-C

1 4 aryl and heterocycle may be 0 substituted with halogen, CI-C 6 alkyl, hydroxy, C 1 -C6 alkoxy, carboxyl, amino, amino acid residue, -PO3H2, -SO 3

H,

-CO-polyethyleneglycol residue,

-CO

2 -polyethyleneglycol residue, -CO-polyethyleneglycol monoalkyl ether residue, -C0 2 -polyethyleneglycol monoalkyl ether residue or -PO 3

H

2 etc.) is attached to the amino group of the compound.

Furthermore, there may be exemplified a derivative in which a substituent such as Ci-C 6 alkoxy, C 6 -Ci4 aryloxy, etc.

(wherein said Ci-C 6 alkoxy or C 6

-C

4 aryloxy may be substituted with halogen, C 1

-C

6 alkyl, hydroxy, CI-C 6 alkoxy, carboxyl, amino, amino acid residue, -P0 3 H2, -SO 3 H, 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.

en"MTP in the small intestine" refers to the MTP existing ci in small intestinal epithelial cells.

o 5 "MTP in the liver" refers to the MTP existing in hepatic C cells.

o00 The expression "selectively inhibit MTP in the small ointestine" means the level of inhibition is at least about C 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 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 c N blood is approximately 8 or more to 1 one hour after the oral J administration to hamsteris i.e. about 80% or more of the agent M (compound) is metabolized before arriving at the liver (see Test Example or on the basis of liver S9 metabolic stability test, O 5 it means that 10 minutes after the test using human or hamster 0\ S9 the remaining rate of unaltered form is about 20% or less, 00 preferably about 10% or less, more preferably about 8% or less o (see Test Example 7).

C 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 Scellulose, hydroxypropyl methylcellulose.

c polyvinylpyrrolidone, etc. Preferable examples of said disintegrating agent include starch, carboxymethylcellulose, 0 5 carboxymethylcellulose calcium, crosscarmellose sodium, h sodium carboxymethylstarch, etc. Preferable examples of said 00 4 solvent include water for injection, alcohol, propylene glycol, n macrogol, sesame-seed oil, corn oil, propylene glycol fatty 0 acid ester, etc. Preferable examples of said solubilizer include polyethyleneglycol, propyleneglycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanoiamine, sodium carbonate, sodium citrate, etc.

Preferable examples of said suspending agent include surfactants 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.

166 0 0 U Preferable examples of said coloring agent include food colors such as food yellow No. 5, food red No. 2 and food blue No. 2, n lake colors for food, iron oxide, etc.

ci O 5 Best mode for carrying out the invention C" Detailed description is given below with respect to 00 various substituents.

SR

1 is preferably hydrogen; CI-C6 alkyl such as methyl, FC ethyl, etc.; CI-C 6 alkoxy such as methoxy, isopropoxy, etc.; halogen such as fluorine, chlorine, etc.; halo C 1

-C

6 alkyl such as trifluoromethyl, etc.; or C 2

-C

6 alkenyl such as isopropenyl, etc.

R

2 is preferably phenyl (which may be substituted with halo Ci-Cs alkyl such as trifluoromethymethyl, etc.; CI-C 6 alkyl such as methyl, ethyl, etc.; halogen such as fluoro, chlorine, bromine, etc.;

CI-C

6 alkoxy such as methoxy, etc.; Ci-C 6 acyl such as acetyl, etc.;

C

2

-C

6 alkenyl such as isopropenyl, etc.; or cyano);

CI-C

6 alkyl such as ethyl, isopropyl, etc.;

C

3

-C

7 cycloalkyl such as cyclohexyl, etc.; CI-C 6 alkoxy such as butoxy, etc.; halo CI-C6 alkyl such as trifluoromethyl, etc.; halo Ci-C 6 alkyloxy such as trifluoromethoxy, etc.; C7-C16 aralkyl such as benzyl, etc.;

C

6

-C

14 aryloxy such as phenoxy (of which aryl moiety may be substituted with halo CI-C 6 alkyl such as trifluoromethyl, etc.), etc.;

C

7 -Cs 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(R 40

(R

41 (wherein

R

40 and R 41 are each independently hydrogen or optionally substituted phenyl).

0

SR

2 is preferably hydrogen or halogen such as chlorine, Setc.

R

2 is preferably hydrogen, halo C 1

-C

6 alkyl such as c trifluoromethyl, etc.; CI-C 6 alkyl such as methyl, ethyl, etc.; O 5 halogen such as fluorine, chlorine, bromine, etc.; Ci-C6 alkoxy such as methoxy, etc.; C 1 -Cs acyl such as methylcarbonyl, etc.; 00

SC

2

-C

6 alkenyl such as isopropenyl, etc.; or cyano.

ci S Ring A is preferably 0 or among which phenyl is especially preferred.

X is preferably -COO-, -N(R'L)CO- or -CON(RO 1 (wherein

R

10 is hydrogen; Ci-C 6 alkyl such as methyl, isopropyl, etc.; or C3-C 7 cycloalkyl such as cyclohexyl, etc. among which -COOor -CONH- is especially preferred.

Ring B is preferably Ci Cfl

N-

or cI N

O

Sor more preferably or most preferably

R

3 is preferably hydrogen; hydroxy; halogen such as chlorine, bromine, etc.; CI-C 6 alkyl such as methyl, ethyl, isopropyl, isobutyl, etc.; substituted

C

1

-C

6 alkyl such as isobutyl substituted with hydroxy, etc.; C 1

-C

6 alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, etc.; halo CI-C 6 alkyl such as trifluoromethyl, etc.;' C,-C 16 aralkyloxy such as benzyloxy, etc.; C-C6 acyl such as formyl, etc.; optionally substituted heterocycle such as 4-methyl-thiazol- 2 -yl, etc.;

-CON(R

1

(R

1 2 (wherein

R

1 and R 12 are each independently hydrogen;

CI-C

6 alkyl such as methyl, ethyl, propyl, isopropyl, etc.; C 6

-C

1 4 aryl such as phenyl, etc.; C-C 1 6 aralkyl such as may be taken together with the nitrogen to form 0 ci alkoxycarbonyl such as methoxycarbonyl, etc.; C.C6 acyl such as acetyl, etc.; or Ru and R" may be taken together with the O

O

-N

N

or (wherein p is th e same meaning as defined above) or -CO) or

CH

2 N(R)(R (wherein R is C-Calky such aisopropyl each independently such as methoy, ethoyydrogen C-C alky such as methyl, ethyl, etc..; C7-C aralkoxycarbnyl such as mehoxyloxy, etc.; .Cor hydroxy) such A lternatively, etc or and RR may be taken together with the nitrogen Sntrogen to which they are attached and ring B to form -N )p -N 0 or 15 0 0 (wherein p has the same meaning as defined above)); or -CO(R 15 S(whereins preferably hydrogen or halogen such as isopropy, etc.; C-C alkoxyrine, chlorine bromine, ethoxy, propoxy, isopropoxy, etc.; C aralkyloy such as benzylene ooxy, ethane-; or hydroy)l.

Alternatively,

R

3 and R' 0 may be taken together with the nitrogen to which R 10 is attached and ring B to form Sis preferably 1 or 2.

R

4 is preferably hydrogen or halogen such as fluorine, chlorine, bromine, etc.

Alkl 1 is preferably methylene or ethane-1,1-diyl.

1 is preferably 0, 1 or 2.

Alkl 2 is preferably methylene.

m is preferably 0 or an integer of 1 to 3.

S D is preferably

CI-C

6 alkyl such as ethyl, propyl, Sisopropyl, butyl, isobutyl, sec-butyl, sec-pentyl, etc.; C 2

-C

6 n alkenyl such as n-propenyl, etc.; C 2

-C

7 alkoxycarbonyl such as ethoxycarbonyl, etc.; -N(R 42 )-CO(R4 3 (wherein

R

42 is hydrogen 0 5 or Ci-C 6 alkyl; R 43 is C 6

-C

1 4 aryl such as biphenyl, etc.; or C 7

-C

1 6 o aralkyl); or a group of the formula shown below: 00 o R6 (wherein ring C, R 5

R

6 and R 7 each has the same meaning as defined above).

Ring C is preferably

C

6

-C

14 aryl such as phenyl, naphthyl, etc.; C 3

-C

7 cycloalkyl such as cyclopentyl, cyclohexyl, etc.;

C

7

-C

16 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 R 7 and R 8 to form

R

5 is preferably hydrogen; Ci-C 6 alkyl such as methyl, etc.; C 1

-C

6 alkoxy such as methoxy, etc.; halogen such as chlorine, etc.; nitro; amino; C 6

-C

1 4 aryl such as phenyl, etc.; or -CON(R 1

(R

17 or -CH 2 -CON(R6)

(R

17 (wherein R 16 and R 1 are each independently hydrogen; Ci-C 6 alkyl such as ethyl, etc., C or halo-C 1

-C

6 alkyl such as 2,2,2-trifluoroethyl, etc.).

SR

6 is preferably hydrogen or halogen such as chlorine, n etc.

R

7 is preferably hydrogen..

0 5

R

8 and R 9 are each independently preferably hydrogen;

CI-C

6 alkyl such as ethyl, etc.; C 6

-C

1 4 aryl such as phenyl, etc.; 00 hydroxy-Ci-Cs alkyl such as hydroxymethyl, etc.; S-CON (R )(R 19 (wherein R 18 and R 19 are each independently C hydrogen;

C

1

-C

6 alkyl such as methyl, ethyl, propyl, isopropyl.

butyl, isobutyl, etc.; C 3

-C

7 cycloalkyl such as cyclohexyl, etc.; halo Ci-C 6 alkyl such as 2,2,2- trifluoroethyl, etc.;

C

2 -C.2 alkoxyalkyl such as methoxyethyl, etc.; or C 6

-C

1 4 aryl such as phenyl, etc.); -COO(R 20 or -(CH2)n-OCO(R 20 (wherein

R

20 is hydrogen; Ci-C 6 alkyl such as methyl, ethyl, propyl, isopropyl, isobutyl, etc.; or C 3

-C

7 cycloalkyl such as cyclohexyl, etc., and n is an integer of 0 or -N(R 21

)(R

22 (wherein R 21 and R 22 are each independently hydrogen; Ci-C 6 alkyl such as methyl, isopropyl, etc.; Ci-C 6 acyl such as acetyl, propionyl, butyryl, etc.; CI-C 6 alkylsulfonyl such as methylsulfonyl, etc.; or R 2 1 and R 22 may be taken together with the nitrogen atom to which they are attached to form 0

-N

0 or R 8 and R 9 taken together may form C 3 cycloalkyl such as cyclopropyl. cyclohexyl, etc.

Preferred embodiments of various substituents and the substitution site will be illustrated below.

SR

1 is preferably hydrogen, halo Cl-C6 alkyl or CI-C6 alkyl, n among which hydrogen is especially preferred.

R

2 is preferably phenyl (which may be substituted with O 5 halo Ci-Cs alkyl such as trifluoromethyl, etc.; CI-C 6 alkyl such 00 as methyl, etc.; halogen such as chlorine, etc.; or Ci-C 6 alkoxy 00 such as methoxy, etc.).

oR R is preferably hydrogen.

SR

2 is preferably hydrogen, halo-Ci-Cs alkyl, halogen, Ci-C 6 alkyl or Ci-C 6 alkoxy, and trifluoromethyl is especially preferred.

X is preferably -COO- or -CON(R 10

(R

10 has the same meaning as defined above), among which -CONH- is especially preferred.

Ring B is preferably phenyl.

R

3 is preferably

CI-C

6 alkyl, Ci-C 6 alkoxy, -CON(R 1

(R

2 (wherein R" and R 12 are each independently preferably hydrogen or CI-C 6 alkyl) or -CO(R 1 5 (wherein

R

15 is preferably

CI-C

6 alkoxy).

R

4 is preferably hydrogen or methyl, and especially preferably methyl.

Alk' is preferably methylene.

Alk 2 is preferably methylene.

1 is preferably 0 or i, especially 1.

m is preferably 1 or 2, especially 1 or 2.

D is preferably

CI-C

6 alkyl or a group of the formula shown below: 173 i o o. R6

R

7 6o (wherein ring C, R 5 R' and R' each has the same meaning as def ined 00 Sabove).

o Ring C is preferably phenyl, pyridin-3-yl, thiophen-3-yl, C 5 thiophen-2-yl and thiazol-2-yl. among which phenyl is especially preferred.

R

5

R

6 and R 7 each is preferably hydrogen, halogen or C 1

-C

6 alkyl, among which hydrogen is especially preferred.

R

8 and R 9 each is preferably hydrogen,

CI-C

6 alkyl, C 6

-C

14 aryl, -CON(R' 8

)(R

1 (wherein RI and R 19 each is preferably hydrogen or C 1

-C

6 alkyl) or -COO(R 20 (wherein

R

20 is preferably hydrogen or C 1

-C

6 alkyl), among which -CON(R 18

(R

19 (wherein

R

18 and R 19 each is preferably hydrogen or Ci-C 6 alkyl) or

-COO(R

20 (wherein

R

20 is preferably hydrogen or Ci-C 6 alkyl) are more preferred, and -COO(R 20 (wherein

R

20 is preferably Ci-C 6 alkyl) is especially preferred.

The substitution site of -(CH2)z- on the benzene ring in the formula 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 enantiomers is in enantiomer excess of o U about 90% or higher, more preferably in enantiomer excess of about 99% or higher.

ci When the compounds of the present invention are used as O 5 an agent for the treatment or prophylaxis of hyperlipidemia or 0 arteriosclerosis, they can be' administered systemically or 00 locally, and orally or parenterally. Though the dose may vary o depending on the age, body weight, symptoms, therapeutic effect, ^c etc., the daily dose per adult is in the range of 0.1 mg to ig 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 ci Co lactose, mannitol, glucose, hydroxypropyl cellulose, Smicrocrystalline cellulose, starch, polyvinylpyrrolidone, M magnesium aluminometasilicate or powdery silicic anhydride.

In the case where the compounds of the present invention are o 5 formulated into tablets or pills, they may be coated with a 0 gastroenteric or enteric coating film containing a substance 00 c such as sucrose, gelatin, hydroxypropyl cellulose or 0 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 triethyl citrate, triacetin, stearic acid, palmitic acid, myristic acid, etc., and derivatives thereof. These additives are suitable ci C for preparing liquid or semi-solid contents. In the capsules Sof the present invention, propylene glycol fatty acid esters en are preferable as such an additive. Examples of the propylene glycol fatty acid esters are propylene glycol monocaprylate 0 5 (Capmul PG-8 (Brand name), Sefol 218 (Brand name), Capryo 190 0 (Brand name), propylene glycol monolaurate (Lauroglycol

FCC

OO

S(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 (Brand 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, 0* c auxiliary agents such as wetting agents, suspending agents, Ssweeteners, condiments, flavors or antiseptics may be added to CM said liquid formulations.

In the case where the pharmaceutical compositions of the O 5 present invention are parenteral formulations such as 0" injections, there are employed sterilized aqueous or 00 Snon-aqueous solutions, solubilizers, suspending agents, Semulsifiers, etc. Examples of the aqueous solutions, solubilizers and suspending agents include distilled water for injections, physiological saline, cyclodextrin, and derivatives thereof; 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 ci or prevention of said diseases are characterized in that they selectively inhibit MTP (microsomal triglyceride transfer n protein) in the small intestine. Among these agents, an agent which does not substantially inhibit MTP in the liver, while O 5 inhibits only MTP in the small intestine is desirable.

0" Specifically, it is preferable that MTP inhibition of the agent 00 in the liver is approximately 1/3 or less, preferably 1/100 or Sless when compared to that in the small intestine as estimated C in terms of ED50 or ED 20 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 compoiund reaching the liver is about 20% or less, preferably less than about more preferably about 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 C or in combination with two or more kinds of said drugs. Examples Sof the antihyperlipidemic drugs include a statin-type drug, m more specifically, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin or cerivastatin. Examples of the O 5 anti-obesity drugs include mazindol or olristat. Examples of 0 the anti-diabetic drugs include insulin preparations, 00 c sulfonylurea drugs, insulin secretion-promotor drugs, o sulfonamide drugs, biguanide drugs, a-glucosidase inhibitors, c 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, p-blockers. a,p-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 hydrochloriae, 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, O amlodipine besylate, felodipine, cilnidipine, aranidipine, Spropranolol hydrochloride, propranolol hydrochloride delayed release, pindolol, pindolol delayed release, indenolol hydrochloride. carteolol hydrochloride, carteolol O 5 hydrochloride delayed release, bunitrolol hydrochloride.

0 bunitrolol hydrochloride delayed release, atenolol, Sasebutolol hydrochloride, metoprolol tartrate, metoprolol Startrate delayed release, nipradilol, penbutolol sulfate, C 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, 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.

o Next, a process for preparing an ester compound M represented by the formula will be illustrated below as an example, but the process of the present invention is not limited O 5 thereto. In the process mentioned below, D is a group of the kn 0C formula 00 (N

RG

SC (2) (wherein ring C, R 5

R

6 and R 7 each has'the same meaning as defined above), and when D is Ci-Cs alkyl. C2-C6 alkenyl, C2-C7 alkoxycarbonyl or -N(R42)-CO(R 4 3

(R

42 and R 43 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 a process for preparing compounds in which X is -CONH-(CH2)nwill be illustrated below7.

Process 1 R2 0 Rl A OH (2) step 1-1 R 3 R 0 0 2 N- (CH 2 B (A 1k 1ko-R 23 (4) j step 1-2

R?

3 R

H

2 N -(CH 2 rt B (AWk 1)k o-R 23 R2 0 A C 1 -step 1-3

RI

1 R2 0 A N- (CH2)

RIH

0 (A I k 1 AO R2 (6) step 1-4 step -KHO- (A 1k' 3 R4 0 A N-(C0 2 B (A Ik 1) 1 0- Riv

H

(1-1) In the above reaction scheme, R 2 R 3 R 4

R

6

R',

R

8 R9, 1, mn, n, Alk', Alk 2 ring A, ring B, and ring C each has the same meaning as defined above and R 2 3 is C 1

-C

6 alkyl.

Step 1-1 A carboxylic acid of the formula is reacted with oxalyl Cn chloride or thionyl chloride in a solvent to give an acid chloride of the formula O 5 The. solvent used in the reaction includes, for example, C ethers such as diethyl ether, tetrahydrofuran, dioxane, 00 1 1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as o benzene, toluene, hexane, xylene, etc.; halogenated C 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 0 C to 120 0

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 is hydrogenated in a solvent in the presence of a catalyst to give a compound of the formula 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 c combination thereof. Preferred solvents in the present Sreaction include alcohols such as methanol, ethanol, isopropyl n alcohol, t-butanol, etc., and a mixture of said alcohol solvent ci and tetrahydrofuran and/or water.

S 5 The catalyst used in the reaction includes, for example, 0 palladium-carbon, palladium hydroxide, Raney-Ni, platinum

OO

oxide, and among which palladium-carbon or reduced iron is Spreferred.

C The reaction temperature is about 0°C to 120 0 C, preferably about room temperature to 100 0

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 is condensed with an amine of the formula in a solvent in the presence of a base to give a compound of the formula 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, C o N-methylmorpholilne, etc.; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, Metc.; and alkali metal carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium o 5 bicarbonate, etc., among which triethylamine, sodium hydroxide or sodium bicarbonate is preferable.

00 N The reaction temperature is about 0 0 C to 80 0 C, preferably about 0 0 C to room temperature.

Ci The reaction time is about 10 minutes to 48 hours, i0 preferably about 30 minutes to 24 hours.

In the case of a compound of the formula wherein

R

23 is hydrogen, a compound of the formula 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 can be prepared by using a condensing agent WSC-HOBT,

DCC-HOBT)

for a compound of the formula and a compound of the formula Further, a compound of the formula may be provided by converting a compound of the formula 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 is hydrolysed in a solvent in the presence of a base to give a compound of the formula 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 ci Spresent reaction include a mixture of tetrahydrofuran and ethanol or methanol. Examples of the bases are aqueous Ssolutions of alkali metal carbonates such as sodium carbonate, potassium carbonate, etc., or aqueous solutions of alkali metal 0 5 hydroxides such as lithium hydroxide, sodium hydroxide, 00 potassium hydroxide, etc., among which sodium hydroxide or 00 lithium hydroxide is preferable.

o The reaction temperature is about 0°C to 120 0 C, preferably Ci about room temperature to 80 0

C.

The reaction time is about 1 hour to 24 hours, preferably about 2.5 hours to 12 hours.

Step This step is a general condensation reaction of a carboxylic acid with an alcohol.

A carboxylic acid of the formula is condensed with an alcohol of the formula in a solvent in the presence of a base and a condensing agent to give a compound of the formula 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 ci O N,N-dimethylformamide.

SExamples of the bases used in the reaction include organic Sbases such as triethylamine, pyridine, dimethylaminopyridine, N-methylmorpholine, etc., among which dimethylaminopyridine o 5 is preferred.

C" Examples of the condensing agents used in the reaction 00 c include 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide Shydrochloride (WSC.HC1), dicyclohexylcarbodiimide (DCC), etc.

c among which 1-ethyl-3- -dimethylaminopropyl)carbodiimide hydrochloride is preferred.

The reaction temperature is about O0C to 80 0 C, preferably about OOC 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 may be converted into its mixed anhydride and then reacted with an alcohol of the formula in the presence of a base.

Process la Process la as shown below is an alternative of Process 1.

o Process la O

R

2

R

4 0n 2 (H 2 B (A Ik') oR23 (4) o *step la-i R3

RA

000 00 A (105) 02 B (AlIk 1) OH step la-2 CV2B HO I k 2

R'

FI~

C

0 N-(CHd B (AlIk 1$0- (A I k2) 2 R8 (106), step la-3R6 R

T

4

C

H

2

N-C

2 )11 Ak1i"O~(~2 R8 (107) 2 0 step 1a-4 A CI (3) A N-0C 2 B (Alk') >&O-(Alk2) RIL ~H 9 189 o (1 In the above reaction scheme, R 1

R

2

R

3 R

R

5 R6. R 7

SR

R

9

R

23 1, m, n, Alk', Alk 2 ring A, ring B and ring C each has the same meaning as defined above.

o 5 Step la-1 In .A compound of the formula (105) can be prepared from a 00 Scompound of the formula in a similar manner to Step 1-4 of SProcess 1.

Ci 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 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 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 in a similar manner to Step 1-3 of Process 1.

Process 2 Among the compounds represented by the formula a process for preparing compounds in which X is -COO-(CH 2 will be illustrated below.

Process 2

R

3

R

4 R24-0-(CH (Alk OH S RT C (8) o- HO-(A I k2) R 00 step 2-1 R6 R2 0-(CH (Ak) -(Alk2). R R9 step 2-2 RB

R?

R3 C HO-(CH )n (Aik )R

O

(A Ikz2) R (11) 2 0 (2) A OH -O step 2-3

RB

2 0 R 0 C A

I

0 B Alk K I k 2) R pH (1-2) In the above reaction scheme, R 2

R

3

R

4

R

5 R6, R,

R

8

R

9 1, m, n, Alk, Alk 2 ring A, ring B and ring C each has the same meaning as defined above, and R 24 is a hydroxy-protecting group (for example, benzyl, p-methoxybenzyl, tert-butyl, trialkylsilyl, etc.).

Step 2-1 J This step is a condensation reaction of a carboxylic acid Cn with an alcohol similar to Step 1-5 of Process 1. A compound of the formula (10) can be prepared by condensing a carboxylic O 5 acid of the formula with an alcohol of the formula in Ch a solvent in the presence of a base and a condensing agent.

00 SThe solvent used in the reaction includes, for example, ci o ethers such as diethyl ether, tetrahydrofuran, dioxane, S1,2-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 tetrahydrofuran, 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 0 C, preferably about 0°C to room temperature.

The reaction time is about 2 hours to 48 hours, preferably ci about 6 hours to 24 hours.

Step 2-2 en This step is a general deprotection method for hydroxy N groups. For example, when R 24 is benzyl in a compound of the O 5 formula the compound of the formula (10) is hydrogenated in a solvent in the presence of a catalyst to give a compound 00 N of the formula (11).

SThe solvent used in the reaction includes, for example, ^c 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 0 C, preferably about O0C 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 in a solvent in the presence of a base and a condensing agent to give a compound of the formula which is one of the objective compounds.

ci CU The solvent used in the reaction includes, for example, ethers such as diethyl ether, tetrahydrofuran, dioxane.

S1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as benzene, toluene, hexane, xylene, etc.; halogenated O 5 hydrocarbons such as methylene chloride, chloroform, carbon 0 tetrachloride, 1,2-dichloroethane, etc.; esters such as ethyl 00 N acetate, methyl acetate, butyl acetate, etc.; and polar Ssolvents such as acetone, N,N-dimethylformamide. dimethyl ^c 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 condensing agents used in the reaction include l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (WSC.HC1), dicyclohexylcarbodiimide (DCC), etc., among which 1-ethyl-3- -dimethylaminopropyl) carbodiimide hydrochloride is preferred.

The reaction temperature is about 0 C to 80 0 C, preferably about o0C 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

R

2 4 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-5,6ci odicyanobenzoquinone (DDQ), etc., followed by condensation with a compound of the formula After removal of the benzyl group from the resulting compound, the deprotected compound is condensed with a compound of the formula to give a compound o 5 of the formula which is one of the objective compounds.

00 ^c Process A SThe following is an example of the process for preparing ci a compound of the formula wherein ring B is 31 (wherein

R

4 has the same meaning as defined above,

R

3 1 is Ci-C 6 alkyl, and V' is 1).

Process

A

<COOEtCODEt COOEt 4 r (13) COOEt

COOH

0 2 N ON 0 N R31 step A-1 2 step A-2 R (12) (14) step A-3 Rs5-X 2 (16) 2 4 COOEt COOH COOEt 0 N 1 I step A-4 2

CN

R31 (17) In the above reaction scheme,

R

31 and R 4 each has the same meaning as defined above,

R

25 is Ci- 6 alkyl,

X

2 and X 3 each is halogen, and Et is ethyl.

ci Step A-i SA 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.

O 5 The solvent used in the reaction includes, for example, 00 ethers such as diethyl ether, tetrahydrofuran, dioxane, 00 c 1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as o benzene, toluene, hexane, xylene, etc.; alcohols such as Smethanol, 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, potassiumhydride, 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 o0C to 120 0 C, preferably about room temperature to 100 0

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,

U

ethers such as diethyl ether, tetrahydrofuran, dioxane, M 1, 2-dimethoxyethane, diglyme, etc.; alcohols such as methanol, ci 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 00 water.

oExamples of the bases used in the reaction include alkali ci 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 0 C to 150 0 C, preferably about 60 0 C to 120 0

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 Alk' 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 obenzene, toluene, hexane, xylene, etc.; alcohols such as methanol, ethanol, isopropyl alcohol, t-butanol, etc.; and cpolar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, etc., and they can be used solely or in combination o thereof. Preferred solvents in the present reaction are 00 N,N-dimethylformamideY etc.

c-i Examples of the bases used in the reaction include alkali 0 metal hydrides such as sodium hydride, potassium hydride, etc.; ci 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 0 C, preferably about room temperature to 100 0

C

The reaction time is about i0 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 SThe following is an example of the process for preparing n a compound of the formula wherein ring B is

SR

4 0 5 (wherein R and R' each has the same meaning as defined above, Ci and 1" is 2 or 3).

.199 Process B in case of 1"=2

R'

Me O2N- y o.

R' step B-1 (19) COOMe COOBn Br (21) step B-2

R

3

R

4 COOMe COOBn 0 2N)

H.

R

3 step B-3 (22)

R

3 (23) in case of 1"=3

R

4

R

3 COOMe COOBn (21) step B-2'

R

3 step B-3' R 3 (23') In the above reaction scheme, R 3 and R 4 each has the same meaning as defined above, Me is methyl, and Bn is benzyl.

Step B-1 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, ,U 200 hydrocarbons such as benzene, etc., and halogenated hydrocarbons such as methylene chloride, chloroform, carbon M tetrachloride, 1,2-dichloroethane, etc., and they can be used ci solely or in combination thereof. Preferred solvents in the o 5 present reaction are methylene chloride or carbon tetrachloride.

00 The brominating agent used in the reaction includes, for oexample, bromine, N-bromosuccinimide, etc., among which N-bromosuccinimide is preferred.

The reaction temperature is about room temperature to 120 0 C, preferably about 60 0 C to 100 0

C

Step B-2 In a similar manner to Step A-i 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-I of Process A, a compound of the formula can be prepared by reacting a compound of the formula (20')(prepared from a compound of the formula 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, ci S1,2-dimethoxyethane, diglyme, etc.; alcohols such as methanol, Sethanol, isopropyl alcohol, t-butanol, etc.; and water; and en they can be used solely or in combination thereof. Preferred solvents in the present reaction are alcohols.

O 5 Examples of the catalyst used for the debenzylation 0 include palladium carbon, palladium hydroxide, Raney-Ni, 00 C platinum oxide, etc., among which palladium carbon is Spreferred.

C The reaction temperature in the debenzylation is preferably about room temperature to 80 0 C, and the reaction temperature in the decarboxylation is preferably 10°C to 150 0

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 can be prepared from a compound of the formula 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 wherein ring B is (wherein

R

4 has the same meaning as defined above,

R

32 is

-CON(R

1

(R

12 in which R 11 and R' 2 each has the same meaning as defined above, and 1' is 1).

Process C

/R"

HN1

COOH

step C-1 (24) sp C- 02N step C-3

O

COOt-Bu COOMe (27) step C-2 COOt-Bu \N COOMe 0 N 0 N

I(

R12 (28) (26) step C-4

RI

2 (29) In the above reaction scheme, R 4 R" and R 12 each has the same meaning as defined above, Me is methyl and t-Bu is tert-butyl.

Step C-1 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 (25) in a similar manner to Step 1-3 of Process 1 to C give a compound of the formula QAlso, a compound of the formula (26) can be prepared by M condensing a compound of the formula (24) with a compound of the formula (25) using a condensing agent (for example,

WSC,

o 5 HOBT). Alternatively, a compound of the formula (24) is o converted into its mixed anhydride, followed by reaction with C a compound of the formula (25) in the presence of a base, to Sgive a compound of the formula (26).

Cl Step C-2 In a similar manner to Step A-i of Process A, a compound of the formula (28) can 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.

ci c) The reaction temperature is about 0°C to 120 0 C, preferably Sabout room temperature to 100 0

C

m The reaction time is about 1 hour to 24 hours, preferably ci about 2 hours to 12 hours.

S 5 Step C-4 h In a similar manner to Step 1-2 of Process 1, a compound 00 C of the formula (30) can be prepared from a compound of the formula (29).

C 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 wherein ring B is (CH T- 33 (wherein

R

4 has the same meaning as defined above,

R

33 is C1-6 alkoxy or C7- 16 aralkyloxy, and 1' is 1).

Process D R26 COOMe (16)

NOH

OH

4 .COOMe N COOH 0 N '26 o-R" step D-2 (33) step D-l (31) (32)

CI

step D-3 step D-4 (34) COOEt step D-5 O-R2 H N COOEt 0-R2 step D-6 (36) (37) In the above reaction scheme,

R

4

X

2 Me and Et each has the same meaning as defined above and R 26 is C 1 -6 alkyl or C7- 1 6 aralkyl.

Step D-1 A compound of the formula (32) can be prepared by reacting a compound of the formula (31) 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-dimthoethoxyethane, 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 206 sulf oxide, etc. and they can be used solely or in combination thereof. A preferred solvents in the present reaction is M NNdimethylformamide.

Ni Examples of the bases used in the reaction include alkali metal hydrides such asodium ~hydride, potassium hydride, etc. and alkali metal carbonates such as sodium carbonate, potassium 00 ci carbonate, sodium bicarbonate, potassium bicarbonate, etc., o among which sodium hydride is preferred.

Ci The reaction temperature is about 0 0 C to 1o 0 0C, preferably about room temperature to 80 0

C

The reaction time is about 2 hour to 48 hours, preferably about 6 hours to 24 hours.

Step D-2.

A compound of the f ormula (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, f or example, ethers such as diethyl ether, tetrahydrofuran. dioxane, 1, 2 -dime thoxyethale, diglyie, 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 0 'C to, 120 0 C, preferably 207 Cl o about room temperature to QThe reaction time is about 1 hour to 24 hours, preferably c about 2.5 hours to 12 hours.

Step D-3 O In a similar manner to Step 1-1 of Process 1, a compound 00 of the formula (34) can be prepared from a compound of the formula C- (33).

0 Step D-4 0 C 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 0 C to '50 0

C,

preferably about 0 C to room temperature.

Step This process is one carbon homologation (Arndt-Eistert synthesis) by a-diazoketone rearrangement (Wolff rearrangement). A compound of the formula (35) is reacted by 208 ci O use of a silver catalyst (for example, silver benzoate, silver Soxide) in an alcohol in the presence of a base to give a compound C of the formula (36).

The solvent (also served as the reaction reagents) used O 5 in the reaction includes, for example, alcohols such as methanol, g ethanol, isopropyl alcohol, t-butanol, etc., and they can be 00 c used solely or in combination thereof. Preferred solvents o (also served as the reaction reagents) in the present reaction 0 C 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 0 C, preferably about 60°C to 120 0

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

-OR

26 can be converted into -OH.

Process E ci o The following is an example of the process for preparing Qa compound of the formula wherein ring B is mR4 ^1 en o 00 3' ci (wherein

R

4 has the same meaning as defined above, R 34 is o 5 -N(R )(R 14 in which R 13 and R 14 each has the same meaning as 0 c defined above), and 1' is 1).

Process E COOt-Bu pF COOMe 4 t-B COeu I (27) 1 COOMe COOMe ON O-S Br N Br step E-1 Br step E-2 r (38) (39)

/R"

HN. Np HNR' R COOMe COOKe (41) 1 ON R H 2 N wARI 3 Itep R 14 step E-3

NR

14 step E-4R14 (42) (43) In the above reaction scheme,

R

4

R

14 Me and t-Bu each has the same meaning as defined above.

Step E-1 In a similar manner to Step A-i 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 ci (39).

0) Step E-3 SA compound of the formula (42) can be prepared by reacting a compound of the formula (40) with a compound of the formula O 5 (41) without or in a solvent and in the presence of a base.

0 The solvent used in the reaction includes, for example, 00 Sethers such as diethyl ether, tetrahydrofuran, dioxane, o 1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as Sbenzene, 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 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 0 C, preferably about room temperature to 1000C.

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 wherein ring B is (wherein

R

4 has the same meaning as defined above and R 35 is

-COO(R

25 in which R 25 is C1-C6 alkyl, and 1' is 1).

Process F

R

4 Cl COOH step F-l (44) t 4 C (46) C step F-2 .(45) (47) COOBn COOBn (48) COOBn step F-3 O 0- 25 step F-4 0 -O-R" (49) In the above reaction scheme, R 4

R

25 and Bn each has the same meaning as defined above.

Step F-I ci SIn 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 M (44).

Step F-2 S 5 A compound of the formula (47) can be prepared by reacting O a compound of the formula (45) with a compound of the formula ^C (46) in a solvent in the presence of a base.

O 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.

The reaction temperature is about -30 0 C to 80 0

C,

preferably about -20°C to'room temperature.

Step F-3 In a similar manner to Step A-I 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 ci o A compound of the formula (49) was reacted in a similar manner to Step 1-2 of Process 1. followed by debenzylation and c decarboxylation to give a compound of the formula In accordance with the alternative process described in S 5 Step 1-3 and Step 1-5 of Process 1, the compounds of the present Oc invention can be prepared from a compound of the formula obtained in the above Step F-4.

Ci Process G The following is an example of the process for preparing a compound of the formula wherein ring B is

R

4

CH

2 (wherein

R

3 and R 4 each has the same meaning as defined above and 1' is 1).

214 Process G (1 0N OH C1 0 2 NCHN2 ON 0N ON 0 O O R step G-1 R 3 step G-2 R3 (51) (52) (53) 00 4 4 (54) step

COO

H

0 2

N

R3 In the above reaction scheme,

R

3

R

4 and Et each has the same meaning as defined above.

Step G-1 In a similar manner to Step 1-1 of Process 1, a compound of the formula (52) can be prepared from a compound of the formula (51).

Step G-2 In a similar manner to Step D-4 of Process D, a compound of the formula (53) can be prepared from a compound of the formula (52).

Step G-3 In a similar manner to Step D-5 of Process D, a compound ci o of the formula (54) can be prepared from a compound of the formula

C)

(53).

Step G-4 In a similar manner to Step D-6 of Process D, a compound O 5 of the formula (55) can be prepared from a compound of the formula 0 (54).

00 SIn accordance with Steps 1-3, 1-4 and 1-5 of the above O 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 In a similar manner to Step 1-4 of the above Process 1, a compound of the formula 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 obtained in the above Step Process H The following is an example of the process for preparing a compound of the formula wherein ring B is R4 (CH 2 13 (wherein

R

3 and R 4 each has the same meaning as defined above and 13 is 0).

216 Process H 0 2

N-(CK

2 B 0- R 2 3 +step H-i (56)

H

2 N-(CH2n (57) 2 0I AlL i- Cl(3 step H-2 R a

R

B -2 (58) step H-3 A N-(CH 2 B OH

H

step H-4 HO-(A I k 2 (59) RR (1-3) 1 2 3 4 5 6 7 In the above reaction scheme, R R R R R R R

R

8

R

9 R 23 Alk 2,ring A, ring B, ring C. m and n each has the same meaning as defined above.

Step H-i ci C 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 Cc (56).

Step H-2 In a similar manner to Step 1-3 of Process 1, a compound 00 of the formula (58) can be prepared by reacting a compound of Ci the formula (57) obtained in Step of H-i (or commercially oS available product) with a compound of the formula 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 Step H-4 In a similar manner to Step 1-5 of Process 1, a compound of the formula which is one of the objective compounds can be prepared by reacting a compound of the formula (59) with a compound of the formula Process

I

The following is an example of the process for preparing a compound of the formula wherein ring B is R4 N/(CH2) 14- (wherein

R

3 and R 4 each has the same meaning as defined above and 14 is 1 to 3).

ProcessI

H

2

N-(C

2

A

ABn (3) step I- 4 R2 NA N-0C 2 R

RI

(61) step 1-2 Ri NH A N-(CN 2 R"3 (62) Xgr. (Al kI) 14 -CUOMe R 2 0 NAAlk) riCOOMB (63)

N-(CH

2 A H step 1-3 (64) A N-CH 2 step 1-4

H

RAR

1

C

HO-CAIk), RI (8) step 0 klO O-(A I (1-4) In the above reaction scheme.

R

2

R

3

R

4

R

5 R R 8 14, mn, n, ring A, ring C, Bn, Me, Alk', Alk 2 and X 2 each 219 ci o has the same meaning as defined above.

Step I-1 SIn a similar manner to Step 1-3 of Process 1, a compound of the formula (61) can be prepared by reacting a compound of o 5 the formula (60) with a compound of the formula 00 Step I-2 c Under conditions similar to Step 1-2 of Process 1, with Sthe 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 I-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,

X

2 -(Alkl) 1 4 -COOEt (in the formula,

X

2 Alk', 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.; oalkali metal alkoxides such as sodium ethoxide, sodium inethoxide, potassium t-butoxide, etc.; alkali metal carbonates M such as sodium carbonate, potassium carbonate. etc. alkali mhetal hydroxides such as lithium hydroxide, sodium hydroxide, o 5 potassium hydroxide, etc.; alkali metal carboxylates such as 00 sodium acetate, potassium acetate, etc.; and alkali metal phosphates such as sodiumnphosphate, potassiumrphosphate, etc. o among which potassium carbonate or sodium hydride is preferred.

The reaction temperature is about 0 0 C to io 0 0C, preferably about room temperature to 100 0

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 f ormula (6 5) can be prepared f rom a compound of the f ormula (64).

Step In a similar manner to Step 1-5 of Process 1, a compound of the formula which is one of the objective compounds can be prepared by reacting a compound of the formula (6 5) with a compound of the formula Process

J

The following is an example of the process for preparing a compound of the formula wherein ring B is

C)

3 00 and 14 is 1 to 3).

In oProcess J

X

2 (Alkl) ,COOMe (63) N NH (63) 02N N-(A k 14-COOMe Sstep 3-i 3 (66) (67) 4 step J-2 ON N-(Alk') 4

-COOH

(68) In the above reaction scheme, R 3

R

4 m Me, Alk', 14 and X 2 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,

X

2 -(Alk)x-COOEt (in the formula X 2 Alk', 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 ci o In accordance with the Step I-4 of Process I, a compound Q of the formula (68) can be prepared from a compound of the formula M (67).

In a similar manner to Steps la-2, la-3 and la-4 of Process O 5 la, the compounds of the present invention can be prepared from 00 a compound of the formula (68) obtained in the above Step J-2.

ci o Process K c The following is an example of the process for preparing a compound of the formula wherein ring B is 4 N--A I k 1) 4 N==a (wherein

R

3

R

4 14 and Alk' each has the same meaning as defined above).

Process K 4 X 2 (Alk COOMe I T(63) 0 2 N NH ON N-(Alki) -CDOMe step K-1 N%3 (69) step K-2 ON N-(AIkl) 4-COOH (71) ci o In the above reaction scheme,

R

3

R

4 Me, 14, Alk' and X 2 each has the same meaning as defined above.

SStep K-1 In a similar manner to Step I-3 of Process I, a compound of the formula (70) can be prepared by reacting a compound of 00 the formula (69) with a compound of the formula (63).

c Alternatively,

X

2 (Alkl) 14 -COOEt (in the formula

X

2 Alk 1 14 and o Et each has the same meaning as defined above) may be used in C place of a compound of the formula (63).

Step K-2 In a similar manner to Step I-4 of Process I, a compound of the formula (71) can be prepared from a compound of the formula 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 wherein

R

3 of the ring B, and R 10 of the X are taken together to form S/(Al 1k'),4- (AI k 1 0

N

0 (wherein

R

4 14 and Alk 1 each has the same meaning as defined above).

ci Process L SR H OHR I(Alk 0-1 O (Ak k R 00 Cstep L-1 0 0 (1-6) In the above reaction scheme,

R

1

R

2 Rs, R 6 R R8

R

9 14, m, ring A, ring C, Alk 1 and Alk 2 each has the same meaning as defined above.

Step L-1 A compound of the formula (1 5) obtained by debenzylation of a compound (wherein

R

2 6 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 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.

ci qo Examples of the bases used in the reaction include organic bases such as triethylamine, pyridine, dimethylaminopyridine, Nc, N-methylmorpholine, etc., among which triethylamine is preferred.

S 5 The reaction temperature is about -20 0 C to 100 0

C,

0o preferably about 0 C to room temperature.

00 The reaction time is about 10 minutes to 4 hours, o preferably about 30 minutes to 2 hours.

0 ci Process M The following is an example of the process for preparing a compound of the formula wherein R l0 is other than hydrogen.

Process M R2 R3 R 4 SN-(CH 2 5 (Al) 0-R23 (6) X2--RI' step M-1 (72) R R 3 R4 0 0 u N-(CH 2 B(Alk') 0--Rz" (73) In the above reaction scheme. R 1

R

2

R

3

R

4

R

23 1, n, X2, ring A, ring B, and Alks each has the same meaning as defined above, and R 10 is Ci-C 6 alkyl or C 3 cycloalkyl).

Step M-1 A compound of the formula (73) can be prepared by reacting 226 o a compound of the formula obtained in the Step 1-3 of Process 1 with a compound of the formula (72) in a solvent in the presence Sof a base.

The solvent used in the reaction includes, for example, o 5 ethers such as diethyl ether, tetrahydrofuran, dioxane, S1i 2-dimt xyhoxyethane, diglyme, etc.; hydrocarbons such as i benzene, toluene, hexane, xylene, etc.; esters such as ethyl o acetate, methyl acetate, butyl acetate, etc.; and polar C solvents such as acetone, N,N-dimethylformamide, dimethyl sulf oxide, 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 0 C, preferably about room temperature to 80 0

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-1.

227.

0 0 Process N S The following is an example of the process for preparing M a compound of the formula wherein

R

e and R 9 are each

-CONH(R'

9 (wherein

R

19 is Cz-C 6 alkyl) C Process N 00 2 R S CoO H C1 (76) C NH 8R' C R- -NHR step N-i step N-2 (74) (75) (77) RS NH

R

6 C NH OH

NH

0 step N-3 (78) In the above reaction scheme,

R

5

R

6

R

7 25 and ring C each has the same meaning as defined above.

Step N-1 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 ci Ssolvent used in the present reaction is toluene containing a catalytic amount of N,N-dimethylformamide.

SThe reaction temperature is about room temperature to 120 0 C, preferably about 50 0 C to 100 0

C.

S 5 The reaction time is about 10 minutes to 6 hours, O preferably about 30 minutes to 3 hours.

Ci Step N-2 SA 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.

The reaction temperature is about -40 0 C to preferably about -30 0 C to room temperature.

Step N-3 229 o A compound of the formula (78) can be prepared by reacting Q a compound of the formula (77) with paraformaldehyde or formalin Ci without or in a solvent in the presence of a catalytic amount of a base.

The solvent used in the reaction includes, for example, 00 ethers such as diethyl ether, tetrahydrofuran, dioxane, C 1,2-dimethoxyethane, diglyme, etc.; hydrocarbons such as o benzene, toluene, hexane, xylene, etc.; halogenated C 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 1000C, preferably about room temperature to 80 0

C.

The reaction time is about 10 minutes to 24 hours, 230 it o preferably about 30 minutes to 12 hours.

In accordance with the above Processes 1, la and 2, the Scompounds 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 00 C Process 0 O The following is an example of the process for preparing a compound of the formula wherein

R

8 and R 9 are each -COOR" (wherein

R

25 is CI-C 6 alkyl).

Process 0 0 R2 0 -0 azOH R 0 step 0-1 0 0 \,25 0 R2S (79) In the above reaction scheme,

R

5

R

6

R

7

R

25 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 Process

P

The following is an example of the process for preparing ci Sa compound of the formula wherein m is 2 or 3. In this process, tert-butyldimethylsilyl (TBS) may be used in place of M benzyl (Bn).

Process P Xi-- (CH)m -OBn 00

R

5

R

8 (82)

R

5

R

O

SR'"tC R-

(CH

2 )m -OBn VR F D R 9 step P-1 RTi._J "R 9 0 0(83) Ci (81) Rs-C (CH)m

-OH

step P-2 (84) In the above reaction scheme, R 5

R

6 R R R9 X 2 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 sulf oxide, etc. and they can be used solely or in combination ci o thereof. Preferred solvents in the present reaction are

C)

QN,N-dimethylformamide or tetrahydrofuran.

M Examples of the bases used in the reaction include alkali metal hydrides such as sodium hydride, potassium hydride, etc.; 0 alkali metal alkoxides such as sodium ethoxide, sodium 00 methoxide, potassium t-butoxide, etc.; alkalimetal carbonates C such as sodium carbonate, potassium carbonate, etc.; and Sorganoalkali 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 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.

o Example 1 m 4-[(4'-Trifluoromethylbiphenyl- 2 carbonyl)aminolphenylacetic acid 2 ,2-bisethylcarbamoyl-2-phenylethyl ester O 5 a) phenylmalonic acid dichloride 01

COCI

C00 OOH

CO

c 00 i COH

COC

C Thionyl chloride (13.7 mL) was added dropwise to a mixture of phenylmalonic acid (11.31 dimethylformamide (230 pL) and toluene (27 mL) under ice-cooling. The mixture was stirred at 80 0 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

H

coc1 0 N COCI -N 0 To a mixed solution of ethylamine in tetrahydrofuran (2M, 45.5 mL), triethylamine (13.9 mL) and methylene chloride mL) was dropwise added the phenylmalonic acid dichloride (8.99 g) obtained in Example 1-a) at -20 0 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 234 o saturated brine, dried over sodium sulfate and concentrated.

The resulting solid was washed with ethyl acetate and hexane C to give the title compound (4.85 g) as a white powder.

c) 2 -Hydroxymethyl-2-phenylmalonic acid diethylamide SH

H

0\ 0 N. 0 N 00

OH

[I H 0' HN 0 N_ 0 I ci 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=1:1 to give the title compound (2.31 g).

d) 4'-Trifluoromethylbiphenyl-2-carboxylic acid chloride CF

CF

3 0 0 OH i CI To a mixture of 4' -trifluoromethylbiphenyl-2-carboxylic acid (5.06 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 temperature 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).

in Se) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]phenylacetic acid ethyl ester

CF

3

CF

3

°N

0- CI HN 0 N 0 OO

H

o To a mixture of 4-aminophenylacetic acid ethyl ester Cl 5 (3.41 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 1N 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)amino]phenylacetic acid CF,

CF

3 o 0

H

H I H The 4-[(4'-Trifluoromethylbiphenyl-2carbonyl)amino]phenylacetic acid ethyl ester (8.12 g) obtained in Example 1-e) was dissolved in 40 mL of tetrahydrofuran and mL of ethanol. After addition of 4N sodium hydroxide (5 mL), 236 Sthe solution was stirred at room temperature for 5 hours and concentrated. The powder formed upon addition of IN

C

c hydrochloric acid was collected by filtration and dried in vacuo to give the title compound (7.48 g).

o 5 g) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]phenyl- 00 acetic acid 2 ,2-bisethylcarbamoyl-2-phenylethyl ester SCF

H

OTH

0 0 N OH

H

N

H

CF

3 N 0 0 0

NH

N HH The 4-[(4'-Trifluoromethylbiphenyl-2carbonyl) amino]phenylacetic acid (519 mg) obtained in Example the 2-hydroxymethyl-2-phenylmalonic aid diethylamide (317 mg) obtained in Example 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 ci o 2-Phenyl-2-{2-[4-(4'-trifluoromethylbiphenyl-2- Scarbonyloxy)phenyl]acetoxymethyl}malonic acid diethyl ester Sa) 2 -Hydroxymethyl-2-phenylmalonic acid diethyl ester 0 0 o COOEt n OH COOEt 00 S 5 Paraformaldehyde (720 mg) was suspended in phenylmalonic C acid diethyl ester (4.73 and a catalytic amount of potassium hydroxide was added thereto at 60 0 C. After stirring for hours, the reaction 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 0 0-

OH

0 0 r 0 Q r OH 0 0 4-Benzyloxyphenylacetic acid (1.09 g) was suspended in methylene chloride (50 mL) and the suspension was dissolved by addition of dimethylaminopyridine (0.511 To the solution was added the 2 -hydroxymethyl-2-phenylmalonic acid diethyl ester (1.20 g) obtained in Example 1-2 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 Sconcentrated. The residue was purified by column Q chromatography on silica gel with ethyl acetate:hexane=l:4 to Sgive the title compound (1.95 g) as a colorless oil.

c) 2-[2-(4-(Hydroxyphenyl)acetoxymethyl]-2-phenylmalonic O 5 acid diethyl ester 00 Ci] 'N n 0to 0 oo i o o o 0' 0 HO 0 0 0 The 2-[2-(4-(Benzyloxyphenyl)acetoxymethyl]-2-phenylmalonic 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-Phenyl-2-{2-[4-(4'-trifluoromethylbiphenyl-2carbonyloxy)phenyl]acetoxymethyl}malonic acid diethyl ester

CF

3 0 OH CF 1 x0 00 0 0

HO

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 ci 2-[2-(4-(hydroxyphenyl)acetoxymethyl]-2-phenylmalonic acid diethyl ester (0.400 g) obtained in Example 1-2 and Sl1-ethyl-3-(3'- dimethylaminopropyl)carbodiimide hydrochloride (0.192 g) was portionwise added thereto. The O 5 mixture was stirred at room temperature overnight and then 0h concentrated. The residue was purified by column 00 ^c chromatography on silica gel with ethyl acetate:hexane=l:3 to Sgive the title compound (0.55 g) as an Ci amorphous powder (see Table 1).

Example 1-3 2-(2-{3-Methyl-4-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid diethyl ester a) 2 3 -Methyl-4-nitrophenyl)malonic acid diethyl ester COOEt O^ COOEt F COOEt 0COOEt N) 0 2N Me Me 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 dimethylformamide (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 dimethylformamide (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 IN 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 opurified by column chromatography on silica gel with ethyl to give the title compound (1.65 g) as a ci yellow oil.

O 5 b) (3-Methyl-4-nitrophenyl)acetic acid SCOOEt 00 COOEt

C

0 0

H

Nn o owN N Me Me Potassium hydroxide (0.168 g) was dissolved in 7 mL of methanol and 1 mL of water, and the 2-(3-methyl-4nitrophenyl)malonic acid diethyl ester (0.250 g) obtained in Example 1-3 a) was dissolved in the solution. The solution was stirred at 100 0 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-phenylmalonic acid diethyl ester 0 0

OH

0 0 0 0 COOH 0- 00N

CO

N

0 0 K OMe MeM The 3 -Methyl-4-nitrophenyl)acetic acid (0.143 g) obtained in Example 1-3 b) was dissolved in methylene chloride mL). To the solution were added 2-hydroxymethyl-2-phenylmalonic acid diethyl ester (0.195 C g) obtained in Example 1-2 4-dimethylaminopyridine (0.090 g) and 1-ethyl-3-(3'- dimethylaminopropyl)carbodiimide n hydrochloride (0.141 and the mixture was stirred at room Ctemperature overnight. The reaction mixture was concentrated S 5 and the residue was purified by column chromatography on silica gel with ethyl acetate:hexane=l: 4 to give the title compound 00 S(0.219 g) as a yellow oil.

Vn d) 2-[2-(4-Amino-3-methylphenyl)acetoxymethyl]-2-phenyl- 0 malonic acid diethyl ester ci 0 0l 0 1 H0N K S0,N H e 0 0 0 2 N 1 Me 10 Me The 2-[2-(3-Methyl-4-nitrophenyl}acetoxymethyl]-2phenyl-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 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-2carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid diethyl ester 242 0 CN CF,

CF

3 Ao o N,

NL

0 0 ,0 0 N 0 0 0 HIN L. H Me 0 0 2 M e Me.

V' In a similar manner to Example 1 4'-trifluoroo 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]-2phenylmalonic 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'-trifluoromethylbiphenyl-2carbonyl amino]phenyl acetoxymethyl)- 2 -phenylmalonic acid diethyl ester a) {4-[Methyl-(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyl}acetic acid ethyl ester CF

CF

3 0 Et A 0 N GEt 0 0 Sodium hydride (51mg) was dissolved in dimethylformamide mL), and the solution was cooled to 0 C. To the solution was added the 4-[(4'-trifluoromethylbiphenyl- 2 243 0 0 carbonyl)amino]phenylacetic acid ethyl ester (500 mg) 1* obtained in Example 1 and the mixture was stirred for one M hour. After addition of iodomethane (183 mg), the mixture was stirred at room temperature for 3 hours and water was then added.

O 5 The reaction solution was concentrated, diluted with ethyl acetate, and washed with water. The resulting solution was Sdried over sodium sulfate and purified by column chromatography Son silica gel with hexane:ethyl acetate=4:l to give the title 0 compound (141 mg).

b) 2-(2-{4-tMethyl-(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenylacetoxymethyl)-2-phenylmalonic acid diethyl ester

CF

3

CF

3 0t 0 0-007 <N

K

CH

3

CH,

The {4-[Methyl-(4'-trifluoromethylbiphenyl-2carbonyl)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 {3-Ethyl-4-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl- 2-phenylethyl ester a) 3-Ethyl-4-nitrophenylacetic acid ethyl ester 0 2- CEl Y0 N ,Et 0 2

N

To a solution of 4-nitrophenylacetic acid ethyl ester 00 l n (1.63 g) in tetrahydrofuran (100 mL) was dropwise added 2M ethyl magnesium chloride in tetrahydrofuran (3 mL) at -15 0 C under Vn 5 argon atmosphere, and the mixture was stirred at the same 0 O temperature for 30 minutes. After further dropwise addition of 2M ethyl magnesium chloride in tetrahydrofuran (3 mL), the mixture was stirred at -15 0 C for one hour, and 2,3-dichloro-5,6dicyano-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 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-2carbonyl) amino]phenyl}acetic acid 2,2-bisethylcarbaroyl- 2-phenylethyl ester

CFI

CO

2 Et 0 2 0 0 NHNj 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 and Example 245 0 1 g) to give the title compound (1.

6 0 g)(see Table 1).

C-)

Examples 1-6 to 1-85 c 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 Sin Tables 2 to 17.

00 cI io Tle 2 to 17 246 aDle I Example Structure iMR (6,300141zCDC1,) I I 1.05(6H, t, J=7.3Hz), 3.l8-3.29(4H, in), 3.53(2,1 4.83(2H, s), 6.95(1H, br-s), 7.02-7.23(8H. m), 7.27-7.36(3H, m), '7.41-7.47(lH, m), 7.49-7.63(4H, m), 7.65-7.72(2H, m), 7.77-7.84(1l, m) 1.19(6, t, J=9.2Hz), 3.53(2H, 4.18(4H, q, 3=9.2Hz), 4.82(2H, s), 6.79(2H, d, 3=12Hz), 7.14(2H, d, 3=12Hz).

7.29(5H, brs), 7.38-7.73(7H, m), 8.09(1H, dd, 3=1.2Hz, 3=7.5Hz).

m.p. 88.4-91.2 1-2

I

1-3 1.21(6H, t, J=7.1Hz), 1.67(3H, 3:47(2H, s), 4.20(4H, q, J=7.1Hz), 4.82(2H, 6.89((1H, brs), 6.92(1K 1 brs), 7.00(11,. d, 3=10.6Hz), 7.30(5H, brs), 7.42-7.84( 91, m).

1.22(6H, t, 3=7.2Hz), 3.23(3H, 3.40(2H, s), 4.21(4H, g. 3=7.2Hiz).

4.83(2H, 6.10(2H, d, 3=8.3Hz), 6.70(2H, d, 3=8.3Hz), 7.07-7.61(13H, m) F- .F 1-4

F

F F

N

0

NH

0- 0 NHKLCHS CH, CH, 0.93(3H, t, 3=7.5Hz), 1.05(6H, t, 3=7.3Hz), 1.94(2H, q, 3=7.5Hz), 3.13-3.28(4H, i), 3.53(2H, 4.83(2H, s), 6.80-7.84(19, m) I in.p. 105-109 1 247 Table 2 Example Structure NmR (6,300MHz,cDC1 2 3.56(2H1,s), 3.65-3.78(2H, PFF sI, 4.55(2H, 5.49(111, br), 7.01(111, brs), 1 0 7.05-7.83(20H, mn).

1-6 0. 0 H-

'NN

ANJ 00 F

F

F 1.39(3H, d, 3=7.2Hz), F F 3.48-3.68(2H1, m), IN 3.70-3.89(2H1, 4.44(111, 1- aH d, 3=10.6Hz), 4.66(lH, d, 170 AH 3=10.6Hz), 5.46(lH, br).

S NN 0 0 NF 6.96U(1H, brs), I >.02-7.84(20H, in).

F

3. 50(2H, s) 3. 68-4 .0O (3H, mn), 4.42(111, dd, F F 'N 1.0Hz), 4.62(lH, dd, F 9, 11. 0Hz) 5. 68 (11, t =6.8Hz), 6.95(111, s), 1-8 A F 7.03-7.17(4H, in), F 7.17-7.36(511, in), 7.44(1H, AJCY 0 N dd. 7.6Hz), 7.48-7.64(4H1, m), 7.65-7.71(2H1, mn), 7.80(111, dd, 3=1.5, 7.6Hz) 1.20(6H, t, 3=7.2Hz), F F -3.51(2H1, 4.20(4H1, q, FN J=7.2Hz), 4.81(2H, s), 'N0 6.92(111, br-s), 1-9 ~0 7.04-7.18(4H1, mn) o 7.24-7.35(5H1. m) 7.44(111.

9 cH, tIC, 3=1.5, 7.1Hz), H Cf% 7.48-7: '64(4H, in), 7.65-7.73(2H1, mn), 7.81(11.

dd, 3=1.5, 7.1Hz) 1.47-1.76(6H1, in), F F 1.90-2.03(2H1. 3.60(2H1, F 3.71-3.85(2H, in), N 4.10(2H1, 6.94(1H.

A-0 0 br-s), 7.12-7.20(414, in), 1-10 0H 7.44(111. Cd, J=1.2, 7.4Hz), 'N NF 7.49-7.64(4H1, in).

H 7.65-7.72(2H1, in), 7.80(111, A FF dd, 3=1.2, 7.4Hz) 248

T

"I

aDle Example Structure NMR (6,300MHz,CDC1 3 1m I 1-11 1.18(6H, d, J=6.4Hz), 1.20(6H, d, 3.50(2H, 4.80(2H, s), 5.08(1H, sept, J=6.4Hz).

5.08(1H, sept, 6.92(1H, 7.05-7.16(4H, 7.27-7.32(5H, m), 7.41-7.47(18, m), 7.49-7.63(4H, m), 7.65-7.72(2H, 7.80(1H, dd, 3=1.5, 7.1Hz) 3.53(2H, 3.74-3.97(4H, 4.87(2H, 6.94(1H, 7.00-7.07(2H, m), 7.09-7.20(4H, m), 7.31-7.47(6H, m), 7.49-7.64(4H, m), 7.65-7.72(2H. 7.80(1H, dd, J=1.5, 1-12 .2 3.51(211.6), 3.71(6H, a).

F F

F

0 0 -0-CH 0 0 0 H CH, 1-13 3.51(2H, 3.71(6H, s), 4.81(2H, 6.92(1H, br-s), 7.05-7.16(4H, m), 7.22-7.35(5H, m), 7.41-7.46(1H, m), 7.49-7.63(4H, m), 7.65-7.71(2H, 7.81(1H, ad, J=1.5, 7.2Hz) 1.20(6H, t, J=7.1Hz), 1.29-1.81(10H, br), 2.40-2.53(1H, 3.52(2H, 4.13(4H, q, J=7.1Hz).

4 .48(2H. 6.93(1H, brs), 7.14(4H, brs), 7.39-7.83(8H, m).

1-14 I_ 4 1.27-1.44(5H, m), 1.46-1.61(3H, m), 1.79-1.90(2H, 3.57(2H, 3.72-3.87(2H, m), 4.07(2H, 5.71-5.81(1H, 6.94(1H, br-s), 7.10-7.21(4H, m), 7.40-7.47(1H, m), 7.49-7.63(4H, m), 7.65-7.72(2H, m), 7.77-7.83(1H, m) 1-15 m.p. 108.8 112.4 m

I

249 Table 'a Example Structure j NilE (b,3004HZ,CDCI,) 1.22(6H1, t, 3=7.2Hz), N 3.57(2H1, 4.21(4H, q, A 0 3=7.2Hz), 4.83(2H4, s), F 7.20(111, d, 3=8.5Hz), FF F 0 0 0- 7.28-7.67(12H, in), 1-16 o, CH 3 7.76(1H, d, J=7.4) H CH 3 93-95 1.20(6H, t, 3=7.1Hz), 1 3.53(2H, 4.19(4H1, q,

A

0 3=7.1Hz), 4.82(2H4, a), 1-170 6.91(1H, d, 3=8.3Hz), 1-7o H 7.11-7.56(161, i), H' 0 0 KH 8.33(1H, dd. 3=7.8, A 1.8Hz), 9.62(111, br.s) in.p. 99-103 1.05(3H1, mn), 1.22(6H1, t.

3=7.2Hz), 1.58(211, m),

H

3 0 1.99(21, mn), 3.57(2H1, s), 1-18 oA- 4 4.21(6H1, mn), 4.85(2H1, s), N N N 8.30(111, in), 10.07(111, N br.s) 1.22(6H1, t, 3=6.9Hiz), N 3.60(2H1, 4.20(4H1, q, I 3=6.9Hz), 4.85(2H., s), F 0 7.12-7.37(9H. in), 1-19 F F A0 7.63-7.73(2H, in), 0>c 7.79-7.86(111, m), N 0 CH, 7.90-8.00(11, in).

1.18(61, t,.3=6.8Hz).

3.51(2H1, 4.17(4H, q, I 3J=6.8Hz), 4.80(2H4, s), A 6.70(21, di, 3=12Hz), 1-20 0 0 A 7.09(21. di, 3=12Hz), 0 o 7.27(5H1, brs), ft 7.41-7.83(8H, mn), A CH, 8.21(111. d, 3=10Hz).

c- Table Example Structure N4R 300MHz, CDC) 1.18(6H, t, J=7.2Hz), n N 3.49(2H, 4.15(4H, q, o J=7.2Hz), 4.80(2H, s), 1 7.07(1H. d, J=8.6Hz), 1-21 o 7.27-7.54(17H, m), SO o 0 7.88(1H, d, J=6.2Hz)

H

00 oo 1.16-1.83(20H, m), F N 3.50(2H, 4.80-4.91(2H, N 4.82(2H, 6.93(1H, S0 br-s), 7.05-7.17(4H, m), 1-22 0 0j7 7.27-7.34(5H, m), N N N 17.47(1H, in), 7.49-7.63(4H, m), 7.65-7.72(2H, 7.80(1H, dd, J=1.5, 7.2Hz) 0.95-1.22(6H, h), 1.23-1.43(4H, m), F 1.50-1.71(6H, m), 0 1.71-1.90(4H, 3.52(2H, 0 3.69-3.83(2H, mn), 1-23 N3 4.84(2H, 6.95(1H, O N 0 br-s), 7.04-7.35(11H, m), 7.41-7.48(1, m), b 7.49-7.65(4H, m), 7.66-7.73(2H, m).

7.77-7.84(1H, m) 3.58(2H, 5.06(2H, s), F N6.81(1H, br-s), 6.99-7.05(4H, m), 0 7.08-7.16(2H m), 1-24 0 7.24-7.47(14H, m), N2o NHN 7.50-7.67(61, 7.80(1H, H Add, J=1.5, 7.5Hz), 9.08(2H, br-s) 1.04(6H, d, J=6.4Hz), 1.09(6H, d, 3=6.8Hz), F F 3.52(2H, 3.95-4.09(2H, F 4.83(2H, s), 0 6.92-7.03(3H, m), 1-250 CH 7.03-7.10(2H. m), 1- o 7.11-7.23(4H, m), N ,N COH, 7.27-7.36(3H, m), HH C 7.41-7.47(11, m), 7.49-7.64(4H, m), 7.65-7.72(2H, 7.80(1H, dd, J=1.5, Table 6 Example Structure 1-26

F

F F

F

FIF

1-27 NMR (6,300MHz,CDC13) 1.19(6H, t, J=7.1Hz), 3.24(2H, 3.59(2H. s), 4.15(4H, q, J=7.1Hz), 4.32(2H, 6.80-6.88(2B, 6.93(1H, brs), 7.11-7.28(7H, m), 7.39-7.83(8H, m) 1.21(6H, t. 3=7.1Hz).

2.14(3H, 3.51(2H, s), 4.19(4H, q, J=7.1Hz), 4.80(2H, 6.87(IH, brs), 6.91-7.02(3H, m), 7.19-7.34(5H, m), 7.40-7.85(8H, m).

3.56(2H. 3.71-3.95(4H, 4.87(2H, s), 6.75-6.83(2H, m), 7.05-7.19(4H, m), 7.29-7.44(6H, m), 7.47-7.60(3H, m).

7.62-7.73(3H, m), 8.05-8.12(1H, m) 3.55(2H, 3.70-3.94(4H, 4.86(2H, s), 6.71-6.79(2H, m), 7.01-7.09(2H, m), 7.11-7.18(2H, m), 7.27-7.54(12H, m), 7.57-7.66(1H, m), 7.94-8.01(1H, m) 0.95(3H, t, J=7.4Hz), 1.45-1.60(2H, m), 1.76-1.88(2H, 3.62(2H, 3.79-3.97(4H, m), 4.08(2H, t, J=6.4Hz), 4.90(2H, 6.99-7.06(2H, 7.10-7.21(6H. m), 7.31-7.41(5H, m), 7.48-7.56(1H, 7.96(1H, dd, J=1.8, 1-28 1-29 1-30 1 1I U~ Table 7 Example Structure NMR (6,300MHz,CDC1) F T 0.97-1.10(6, 1.12(6.

c F F t, 3=6.8HZ), 1.54-1.78(4H, 2.05-2.17(IH, m), N 0 3.54(2, 4.13(4H, q, 1-31 0 0 3=6.8Hz), 4.50(2H, s), 0f0 6.93(1K, brsl, 7.14(4H, c brs), 7.40-7.82(8H, m).

00

H

kn 3.51(211, 3.85(4H. 4.86(2H, 6.88(lH, s), 7.00-7.54(19H.

M),

7.89(11, i) 1-32 H N H H

F

FF

3.56(2H,5s), 3.84(4H. m), N4.86(2H, 6.91(1. d, J=8.3Hz), 7.07-7.55(18H, 1-33 0F im), 8.32(11, ad, =7.9, 1-3 N 0 1.9Hz), 9.64(11, s)

FF

1.23(6H, t, J=7.1Hz), F 3.70(2H,s), 4.22(4H, t, J=7.1Hz), 4.81(2H, F F A 7.02(111, brs), 1-34 0 7.13-7.97(16, m).

N NN' 0 0 H3 0.85(6H, t, 3=7.5Hz), F F N1.37-1.51(4, m), F 3.13-3.22(4H, 3.53(2H, o 4.84(2H, 6.96(1H, 0 7.02-7.09(2H, m), 7.10-7.24(6H. i), N N 0CNHHH 7.27-7.35(3H, m), 7.41-7.47(11, m),

CH

1 7.49-7.63(4.

M),

7.65-7.-2(2H, 7.80(1H, i.p. 100.5-104.0 dd, 3=1.6, 253

IJ

able Example I St=ucture UMR (8,300M~zCC1,) 1 1-36 1-37 2.73(6H, d, Jt4.9HZ), 3 .53(2H, 4.81(2K, 6.94(1H.

br-s), 7.01-7.09(4H, n), 7.11-7.21(4K, n), 7.27-7.35(3H, n), 7.41-7.41(1K, i), 7.49-7.63(4H,

M),

7.66-7.72(2H. 7.81(1H, dd, 3=1.5, 1.20(6H, t, 37 OHz), 3.50(2H, 4.21(4H, q, 3=7.0Hz), 4.90(2H, 6.93(1K, br-s), 7.04-7.15(4. m), 7.15-7.21(1H, m), 7.38-7.47(2H, m).

7.49-7.64(5H, m), 7.66-7.72(2H, m) 7.81(H, dd, 3=1.5, 7.5Hz), 8.46-8.51(1H, ml 1.22(6H, t, J=7.2Hz), 3.51(2H, 4.21(4H, q, 3=7.2Hz), 4.82(2K, 6.98(1H, br-a), 7 .03-7.17(4H 7.22(1H, dd J=5.0, 8.5Hz), 7.41-7.47(1K, 7.48-7.63(5H, i), 7.64-7.72(2K, m), 7.77-7.83(1K, m), 8.50-8.57(2K, m) 1.04(6H, t, 3=7.4Hz), 3.16-3.29(4H, 3.55(2H, s), 4.84(2H, 6.75-6.83(2H, m), 7.04-7.14(4H, m), 7.17-7.22(2K, m).

7.27-7.35(3H, m) 7.41 ad, J=1.1, 7.6Hz), 7.47-7.54(2H, 7.56(IH, dd, 7.6Hz), 7.61-7.72(3H, m), 8.08(1H, ad, 3=1.1, 7.6Hz) 1.20( 6H, t, J=7.1Hz). 3.55(2H, 4.21(4H, qj-J=7.lHz), 4.84(2H, 7.20-7.77(16K, 8.16(111, br) 1-38 1-39 F F

F

0 0 0 0. N 0R 1-40 I I Table 9' Example Structure NMR (b,300MHz,CDC13 1. 01(3H, t, J=7.2HZ) 1.60(2H, Cfl in), 1.96(2H, 3.59(2. s), 3.84(4H, 4.21(2H. t, 3=6.5Hz), 4.89(2H, s).

1-41 O<HN.. F 7.00(1H, d, J=8.3Hz), Nn o Nil F 7.09-7.16(5H, i).

H -7 7.32-7.58(H. 8.26(l, dd, 00 3 8 1.9Hz), 10. 07(1H, br. s) O.88(6H, t, 3=7.1Hz), o F Fn 1.19-1.34(4H. M) I 1.35-1.48(4H.

3.16-3.26(4H, 3.52(2H, C A 4.84(2H, 6.95(1H. br-s).

1-42 H N 7 .02-7.23(8H, m) 7.27-736( 3 C1% 7.40-7.47(1. m), 7-49-7.63(4H. m) 7.64-7.73(2H, 7.81(1H, dl. J=1.5, 1.22(6H, t,3J7.1Hz) 3.58(2H, 4.22(4H, q. J=7.lHz), 4.85(2H, 6.23(2H, d, 1-43 3=8.5Hz), 7.30-7.73(10H. i), 0 A 1 AO 7.87(2H. d, J8B. SHz) 8.36(111, H H C dd. 3=6.8, 2.3Hz). 12.3(1, CH, brs) 1.24(6H, t. J=7.1Hz). 3.58(2H.

4.23(4, 3 3 =7.Hz), 0 4.27( 2 H, 4.8(2H, s), 67(4 br7.22(2H J=8.5Hz), 1 692-7.8(1711, 7. 61 (2H, d, H CH. 1. 05(6H F t J=7 .3Hz I 69 (3H, F6 3.14-3.30(4H. m), 3.49(2H,s),4.83(214, s), 6. 77 1H, brs) 6. 89 (rH, brs) 6.92-7.85(17H, m).

e ii UI aDle 1z EFample Structure NMR (8,30 OMHz, CDC1,)

I

1.20(6H, t, J=7.1Hz), 2.38(38, 3.49(2H, 4.19(48, q, o 3=7.1Hz), 4.81(2H, s), 1-46 ~6.90(11, brs), 7.05(4H, brs), 7.19-7.56(12H, 7.88(11, d.

N 0 0=7.1Hz).

HICN N 1.20(6H, t, J=7.1HZ), 3.49(2H, 3.81(3H, 4.19(4H, q, N J=7.1Hz), 4.81(2H, s), S- 6.87-7.56(17, 7.86(1H, d, 0 J=7.6Hz) N NH 1.12(6H, t, 3=7.2Hz).

2.49-2.58(2H. m) 3.30(4H, dg.

3=5.6, 7.2Hz). 3.54(2H, s), 4.07-4.15(2H, 6.94(1H, 4 0 Abr-s), 7.11-7.18(4H, m), N 0 7.22-7.37(5H, m), A CH 7.41-7.46(1H, m), 7.48-7.63(6H, m), 7.65-7.7(21, 7. 8(11, dd, 3=1.5, 0.87(6H, t, J=7.2Hz) 1.51(4H, tq, J=7.2, 7.2Hz), F F 2.50-2.59(2H, m), 3.18-3.27(4H, m),3.54(2H,s).

A0 0 4.07-4.15(2H, 6.95(18, 1-49 I br-a), 7.12-7.18(4, mn), A C C 7.23-7.36(5H, m), 7.41-7.46(11, m), 7.48-7.63(6H, m), 7.65-7.71(2H, m).7.80(1H, dd.

3=1.5, 1.05(6H, t, 3=7.1Hz).

N3.17-3.28(4H, 3.51(2H, s), N 4.82(2H, 6.87(1l, br-s), 1-50 A 6.97-7.22(8, i), I 0 0 7.27-7.35(31, m), N K cS 7.39-7.59(8H, 7.90(1H, dd, H CH. 3=1.5, cl Table 11 Example structure %NMR (b,300MHzCDC 3 1.03(6H, t, 3=7.lHz), Cfl 3.16-3.28(4H, 3.56(2H, 1-51o), 4.82(2H, s), 5 06.B8-6.94(1H. m).

1-51 1-7.02-7.34(13, m), In 0 7.39-7 49(3H, m).

07.517.59(2H, 8.34(1lH 00 dd, J=1.9, 7.9Hz), 9.63(lH,.

br-s) 1.05(3H, t, 3=7.2HZ), 0n I1.07(6H, t. 3=7.2Hz), 0 1 1.54-1.68(2H, i), l tC 1.92-2.05(2H, m), 3.19-3.31(4H, 3.58(2H, 0 1_q 4.23(2H, J=6.4Hz).

K 4.85(2H, 7.02(1H, d, N ar, J=8.3Hz), 7.06-7.38(10H m).

N, H 7.44-7.53(11, m), 7.57-7.65(2H, 8.30(1.

dd, 3=1.9, 7.9Hz), 10.08(1H, br-s) 1.23(6H, t, 3=7.1Hz), F3.53(2H, 4'.23(4H, q, 3J=7.1Hz), 4.84(2, s).

6.95(1, brs), 7.10(2H, d, 1-53 =8.3Hz), 7.17(2H. d, N C3 NV 'NV I =8.3Hz), 7.32(5H, bra), 7.41-7.87(8H, m).

1.19(6H, t, J=7.1Hz), 3.50(2H, 4.16(2H, q, J=7-Hz), 4.17(2H, q, 1-54 0' J=7.Hz), 4.80(2H. s), 1-4 6.89-7.90(17, m) 1.05(61, t, 3=7.2Hz), 3.19-3.31(4H, 3.54(2H, 4.86(2H, 6.90(1H, d, 0 3=8.3Hz), 7.02-7.11(3H, m)7 7.16-7.23(2H, m), 0 I7.25-7.36(4H, 7.41(1H, 0-91 O d, 3=1.2, 7.5Hz), C1 7.48-7.61(3H, m), 7.62-7.71(3H, 8.21(1H, cd, 31.5, 257 cl Table 12 C) Example -Structure NIR (5,300MHZCDC13 1.21(6H, t, 3=7 Hz) 3-51(2H, 4.20(411, q, 3=7.1Hz).

IS 4.82(2H, 6.99-7.57(16H, 0 in). 7.84(1H, d, 3=7.2Hz).

N

oH 1-5 00 1. 23 (6H, t, J=7.2Hz) 3.57 (2H, Nn 4.22(41, q, J=7.2Hz), I 0 4.85(H, 7.19-8. 08( 19H, M) 1-57 0 iN 0 4,l 0.94(6, d, 3=6.8Hz), 1.22(61H.

F F t, 3=7.1HZ), 3.40(2H, S), S4. 20(4H, q, J 7.1Hz) 4 .82 (2H, 0 4.99(11. 6.16(1H, 1-58 A H*N br.s),6.7 8 2 H, d, 3=8.6Hz), 0 N o 7.08(1l, ad, 3=8.6, F )9 7 20 -7.74(13H, n) 0.89(4H, 1.22(6H, t.

F F J3=7.1Hz), 1.2B-1.78(6H ml, 3.40(2H, 4.20(4H, q.

0 0 0 lj=7.Hz), 4.62(lH, M) b. 1-590 4.82(2H, ?bi 6 br.s), N 0, 6.75(2H, m) 7 .06-7.74(14H, m) 1.23(6H, J=6.9Hz), 1.28(6H, d, 3=6.9Hz), 3.40(1H, sep, 0 J=6.9Hz), 3.56(2H, a).

1-60 N, CH, 0 4.22(4, g, 3=6.9Hz), 4.84(2H, 1-60 IV\ -cns), 7.12-7.614 m I J Table 13 Example Structure NR (b,300MHzCDC1) l.22(6H. t,3 =7.1Hz), 3.53(2H, CC) 4-22(4H, q, J=7.lzz) A 4.23(2H, 4.83(2H, s), 1-61 -1 0 6.98-7.61(19H, m) %0 00 0 4 .10(4H t',36.6HZ) 4.83(2H, o 0 6.93(3-H, brs), 7.08(2H, d, 1-62 0 3=8.6Hz), 7.13(2K, d, AI 3 =8.6Hz), 7.29(5H, brs), H N 7.4Q-7.83(8Hin).

H.0 0.84(12H. 3=6.6Hz), F F1.ao5-1.97(2, 3.50(2H, s).

F F.92(4H, d. J=6.6HZ). 4.84(2H.

N 6.93(1K, brs), 7.08(2H, d, 1;63 A zJ=5.5Hz), 7.13(2H, d, -1 C J=5.5Hz), 7.29(5H, brs), 4.4(K a) .2(Kd A 7.40-7.84Hz, d. 1 22(6H, t, J=7. 3Hz) 3 .57 62, s.2(4H, 2

H.

4.84(2H, 7.21 7.(2H, d, 7. 84(H, a 1 -6 4 F> 057.5 (2H, d, 5 3=8.4Hz) 00, .44-7.4, inHz), 7.5(2KH, 3=84).761Kbr) 7.84(3HK, d. =7.6Hz)1 1. 50-1.69 m) 4. 23 q, J=7. IHz) 4. 25 (H, -e~i J=6.7Hz), 4.84(2H, 1-65 0 7.19(2H, J=8.4H z),(1B -Y -7.37(5HHz, 1236H 7.21.H) 12-14(8,m 0 \-CR 7.44-.6 4(3H, 7.5(2H, d,, q.J=.4Hz), 7.64(H, bs), 7.95(lH, d, J=7.6Hz) Table 14 Example structure WHMt 300MHZ, CDC1 3 cn 0.84(12H, 3=6.8Hz).

1.63-1.79(2H, in), F F N 2 9 7 -3.15(4H, 3.52(2H1.

I

F 4.86(2H1. 6.94(111, br-s), 0N0 7 .01-7.08(2H, m, In1-66 NrC-nY 7.10-7.25(6H, in), o a~H 1 S7.27-7.36(3H, mn), 00 16 H HC 7.40-7.47(1%, m), N CH 7.48-7.63(4Hn) 7fl.64-7.72(2, mn) 7. 80(111, dd, 0 3=1.5. o 087(12H, d, 3=6.8Hz), 1.27-1.38(4H, mn).

F F N1.46-1.61(2H1, in).

F 3 .18-3.28(4H, m),3.52(2H, s), N0 4.84(2H1, 6.94(111, br-s), 1-67 07.01-7.22(81. n) A 7.27-7.35(3H 1 7.41-7.47(11, i) H~C ~i 7.49-7.63(4H, i) 7.65-7.72 (2H, in) 7. 80 (1H, dd, 3=1.5, F 1l.07(3Ho t, 37.21Z), 1.22(6H1, FF NJ7lz,34(H 0 A 3.72(2H,q,3=7.2H2'L,4.

2 0 4

H,.

1-8C0 ct 6.14(2H1, d, 3=8.3Hz). 6.74C2H, N N 0 0 0 d, 3=8.3Hz). 7.07(1H. dd.

K~ 3=9.1, 1.5Hz). 7.23-7.61(12H,.

1.09(6H, t, 3=7.1Hz).

N

1 26 50( 6Hm) 81(4H, M)

A

0 2.99(1H. in), 3.26(4H1, dq, AON ci 4.85(2H,. 7.10-7.42(14H, N ~F m 7.56(2H, d. 3=8.3Hz) 1.05(H t, =7.2Hz).

3 18-3.30(4H,im), 3.53 (2H, s), CI 4.83(2H,. 6.93(111. br-s), N 0 7.02-7.23(811. m), 1-70 A 00 7.27-7.36(3H, mn).

7.37-7.45(5H1, m), N N Ia3 0N H 03 J=1.1, 260 T'ale 13 Example struture NMR 30MHZ, CDC,) 1.05(6H, t, 3=7.2Hz), I 3.18-3.30(4H, 3.54(2H, s), 0i .r 4 .84(2H, s),7.2-7.14(5H, i) 11 0 07.17-7.35(8H, m), 7 3 7 -7.62(5H, 7.74(1H, dd, 0 0

H

H N K J=1.5, 0.85(6H, t, J=7.5Hz), 1.44(4H, tq, J=7.5, 7.5Hz), 1.68(3H, 3.12-3.22(4H, 3.49(2H, 0 s),.4.85(2H, 6.77(1H, A Abr-s), 6.87-6.92(1W i).

1-72 6.94-7.01(1, m), N N 7.11-7.25(4H, m), 7.27-7.36(3H, i).

7.40-7.47(lH, m), m.p. 126.4-127.8 7..50-7.73(6H, Mn).

7.75-7.85(2H, m) 3.29 (6H, s) 3.36-3.48 (8K. m) F 3.53(2H, 4.85(2H, s), 6.971H, 7.04-7.18(4H, A-73 7.19-7.40(8H,

M),

1-73 N H H\ 7.41-7.47(-H, M), H

K

1 7.49-7.64(4H, m), 0, K 7.66-7.73(2H, m), 7.77-7.84(1H, i) 1.22(6H, t,3J=7.1Hz), 2.78(3H, F F 3.52(2H, 4.21(4H, q,

FN

3=7.1Hz), 4.82(2H, s), 0 7 .11(2H, d, J8.5HZ 7.19(2H, 1-74 0 d,0=8.Hz) 7.20-7.35(6H, m) N 0 0 c 7.77(2H, d. 3=8.3Hz), 7.86(2H, s H d, J=8.3Hz) HFc 1.06(6H. t.J=7.3Hz) 2.78(3H, F s),3.20-3.29(4H, 3.55(2H, 4.84(2H, s), 6.98-7.34(12H, 7.77(2H, d, 3=8.3Hz) 7.86(2H, d, J=8.3Hz)

I

261 Table 16 L Example Structure 1-76 1-77 NMR (b,300HHzCDC1a) 1.06(6H, t, 3=7.3Hz), 3.19-3.28(4H, m) 3.54(2H, s), 4.83(2H. 6.99-7.48(13H.

7.71(2H, d, J=8.2Hz).

7.86(2H, d. 3=8.2Hz), 8.05-8.13(1H, m), 5.75-8.84(H, m) 1.06(6H, t, J=7.2Hz), 1.64(3, 3.12-3.33(4H. m) 3.51(2H, 4.84(2H, 6.84(1H, bra), 6.91(lH, bra).

6-98-7.98(121, 8.16( 11 d 3=B.1Hz), 8.84(1l, d.

3=4.4Hz).

0.92(3H, t, J=7.5Hz) 1.20(6H.

t, 3=7.1Hz). 1.94(2H, q, 3=7.5Hz). 3.50(2H, s), 4.20(4H, q, J=7.1Hz), 4.82(2H, 6.79-7.83(17H, m) 0.96(6H, d, 3=6.6Hz). 1.05(6H, t, 3=7.1Hz), 2.15(2H, sep.

J=6.6Hz), 3.19-3.29(4. i), 3.54(2H, 4.83(2H, s), 6.81-7.84(19, im) 0.96(6H, d, 3=6.8HZ), 1.20(6H, t, 3=7.lHz), 2.16(2H, sep.

3=6.8Hz), 4.20(4H, q, 3=7.1Hz), 4.82(2H, S).

6.79-7.82(17H, m) 1-78 1-79 1-80 in.p. 91.5-94.8 1 262 Table 17 Example Structure

F

n.p. 147-158 NMR (,300MHz,CDC1) 0.95(3H, t. J=7.7HZ). 1.13(6H, t, 3=7.2Hz). 1.99(2H, q.

3=7.7Hz), 2.54(2H, t, 3=7.9Hz), 3.20-3.38(4H. i), 3.53(2H, 4.11(2H. t, 3=7.9Hz), 6.79-7.84(19H, m) 0.

7 2(6H, d, J=6.6HZ). 1.06(6H, t, J=7.2Hz). 1.26- 1.44(1H, 1.89(2HF d, J=7.3Hz), 3.20-3.27(4H, 3.52( 2H, s), 4.83(2H. 6. 82-7.88( 19H. m) 0.71(6H, d. J=6 .5Hz), 1.21(6H, t, J=7. Iz) 1. 2-1.43(IH, m) 1.88(2H, d, J=7.3Hz), 3.49(2H, 4.21(4H, q, J=7.lHz), 4.83(2H, 6.79-7.87(17H, m) 1.

2 1 6 H, t, 37.2HZ), 3.48(2H, 4.22(4H, g, J=7.2Hz), 4.83(2H, 7.08(1K, d, 3=8.7Hz), 7.12(11, s), 7.25-7.67(13H, 7.84(11H, dd, 3=1.5, 7.5Hz), 8.37(1. d.

3=8.7Hz) 1.21(6H, t, 3=7.1HZ).,3.

4 8 2

H,

4.22(4K.,q. 3=7.1Hz), 4.83(2H, 7.13(11. d, 3=7.9HZ). 7.28-7.67(14H, i), 7.82(1H, dd, J=1.5. 8.35(11, d, 3=5.7Hz) m.p. 80-86

I

C( Example 2 ({3-Dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2n carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2phenylethyl ester a) 5-Chloro-N,N-dimethyl-2-nitrobenzamide

CI

S0NJ 02 N N 2N O C00H 0 NMe 0 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 CO, tBu 'N 1 CO, ,Me 0ON 0N 0 2NMe 0 NMe 2 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 the mixture was stirred for one hour, and the dimethyl-2-nitrobenzamide (1.0 g) obtained in Example 2 a) was added thereto. The mixture was stirred at 70 0 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:l to give the title compound (1.29 g).

M c) 3 -Dimethylcarbamoyl-4-nitrophenyl)acetic acid methyl ci ester OCO 2 tBu CO Me o 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 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 O COzMe COMe OzN Hz

N

0 -NMe, 0 NMe, 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 265

CF

CO

2 Me

OH

2 MeI H 0 2 NMe 2 N 0 SThe (4-amino-3-dimethylcarbamoylphenyl)acetic acid 00 Smethyl ester (627 mg) obtained in Example 2 d) was subjected o to reactions similar to those in Example 1 e) and Example 1 f) to give the title compound (1.07 g)(see Table f) {3-Dimethylcarbamoyl- 4- -trifluoromethylbiphenyl-2carbonyl) amino]phenyl)acetic acid 2,2-bisethylcarbamoyl-2phenylethyl ester CF3 0 NHO NHEt OH NHEt

CF

3 O o 0 NHEt I H A MeN 0 The 3-Dimethylcarbamoyl- 4 -trifluoromethylbiphenyl-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).

o 0 SExamples 2-2 to 2-119 M Compounds of Examples 2-2 to 2-119 were obtained in a csimilar manner to Example 2. The compounds thus obtained were 0 5 shown in Tables 18 to 41. In addition, compound of Example 2-17 O e) was obtained in a similar manner to Example 2 e) and the

OO

i compounds thus obtained were shown in Table ci o% oD Tame l Example Structure NMR (8,30o.Hz,CDCI 3 1.07(6H, t, J=7.2Hz), F F 2.85(3H, br.s), 2.95(3H, br.s), 3.26(4H, dq, J=7.2, -7.2Hz), 3.54(2H, s), 2 PH ci 4.84(2H, s), H 0 0 7.04-7.68(17H, m), N O8.37(1H. d, 3=8.3Hz).

SHC9.16(1H, br.s) 0.86(611, t, 3=7.2Hz), F 1.46(4H, tq, J=7.2, 7.2Hz), 2.85(3H, br.s), 2.95(3H, I J br.s), 3.19(4H, dt, 3=7.2, 2-2 H7.2Hz), 3.54(2 s) H 4.85(21, s), H 7.03-7.6817H

M),

0 H N'O CH3 8.37(1, d, 3=8.7Hz), ol, 9:17(1H, br.s) 1.07(61, t, 3=7.1Hz), F FN F I 2.83(3H, d, J=4.5 Hz), 3.24(4H, dq, J7.1, '7.Hz) 3.59(2, 4.80(2H, s), 2-3 0 PH 0% o 7.10-7.76(18H1, m), N 8.53(1, d, 3=8.3Hz), H. 11.55(IH, br.s) HN 071-.7(8 H 1CH F F 1.12(6H, t, 3=7.3Hz).

F 2.53(2H, t, 3=7.7Hz), 0 2.86(3H, brs), 2.95(31, 0 brs), 3.20-3.40(4H, m), 2-4 m3.54(2H, 4.12(2H, t, 2-4 N0 K=7.7Hz), 7.09(1H, brs), a3i, 7.17-7.75(14H, m), 8.36(1H, d, 3=8.4Hz), 9.24(1H, brs).

m.p. 128-129 1.21(6H, t, 3=7.1Hz), FF 2.81(3H, brs), F I 0 2.92(311,brs), 3.50(2H1, s), 0> 4.20(41, q, 3:7.1Hz), 0 C3 4.82 (2H, s) 6.99(IH, brs) 07.17-7.71(14H, m), 2- C8.33(11, d, 0. N9.14(11, brs).

I m.p. 114-116 1 268 *1 :aDie 19 Example Structure I NMR L6.300MHZ,CDCL 3 0.98(6H1, t, 3=7.3Hz), F F N.3.12(4H,. dg, J=7.3, 7.3Hz), F A 3.58(2H1, 4.50(2H1, d, A 0 o J~ =5.9Hz), 4.79(2H1, s), AHH CH, 7.O1-7.59(16H, m), 2- ~0 0 KH 7.72(111, dd, J=7.0, 1.8 Hz), N~r 8.23(111, 8.51(111 d, 0 4 3=8.5Hz), 11.49(111, br.s) 1.07(6H, t, 3=7.3Hz).

F F 1.66(2H, mn), 2.28(2H1, m), N

A

0 2.87(3H1, br.s), 2.93(3H1, br.s), 3.24(4H, dg, 3=7.3, 2-7 0 H 7.3Hz), 3.57(2H1, s), N H 4.11(2H1, t, 3=6.9Hz).

14 7.13-7.66(17H, in), A HF.

1 4 ~8.36(111, d, 3=8.4Hz), 9.08(111, br.s) F F 1.08(6H, t, 3=7.2Hz), F N0.98-1.21(6H1, brd).

0 3. 26 (4H, dq, J=7 .2 7 .2Hz) A 3.12-3.51(4H, brd).

2- 1 0 M C 3.56(2H, 4.84(2H1, s), 2-8 N 0 0 K 7.06-7.63(17H1, in).

N N 8.21(111, d, 3=8.7Hz), A a N0)418.88(111, s) 1.07(6K, t, 3=7.1Hz), FF 0.93-1.59(6H1, brd), N0 3.26(41, dq, 3=7.2, 7.2Hz), A 3.56(2H1, 3.41-3.95(2H, 2-9 N 0 0 m\C brd), 4.84(21.

N k- s),7.01-7.62(17H. mn), A N 8.08(111, d, 3=8.3Hz), H,.C 05 8.70(111, br.s) m.p. 108-117 1.21(61, t, 3=7.1Hz), F F N0.95-1.27(6H, brd).

N 0 3.08-3.49(4H1, brd).

A A 3.52(2H1, 4.21(4H1, q, 2-10 N 0 J 37.1Hz), 4.83(2H, 04 s),7.06(IH, d, 3=1.9Hz), A AN 7. 19(1H1, dd, 3=8. 7, 1. 9Hz) 0 11 04 7.31-7.63(13H, in), F3 8.19(111, d, 3=8.7Hz), 8.90(111, br.s) cl Table oExample Structure NMR (8,300MHzCDC1 3 1.21(6H1, t. 3=7.1Hz), F F 1.00-1.52(12H, brd). 3.52(2H, F 0 3.49-3.92(2H, brd), 0 o 4.20(4H. q, 3=7.1Hz), 4.82(2H, 2-11 D o 7.02(14. d, 3=1.9Hz), Oi 1N 7.17(11. dd, 1.9Hz).

.7.31-7.64(13H, 8.06(1H, a 00 3=8.4Hz) 8.72(18. br-s) 00 N-C CH.

CF 1.01-1.21(6. 1.07(6H, t, F=7.3Hz), 2.78(3-. brs).

0 3.20-3.31(4H, 3.56(28.

Cl s 3.82-4.27(1H, 2-12 N y 4.84(2H, 6.99-7.63(17H, A NA 0 0 H 8.19(1H, d, J=8.4Hz), H3C 0 8.98(1, br.s) HC 01, 0.9-1.27(3H, br) 1.21(6, t, p F N=7.1Hz). 2.73-2.96(3H, br).

3.05-3.49(2H, br), 3.51(2H, N 4.21(4H, q, J=7.1Hz), 074.82(2H. s) 00-7. 08(H, m) 2-13 N 0 0 7.19(1H, dd, J=1.9. 8.3Hz), 21 N I'll,3 7.24-7.36(5, m) .7.39(1. dd, o N 7.9Hz). 7.43-7.70(7H, 8.28(11, d, 3n8.68z), in.p.116.5-ll 9 .O 8.92-9.18(1, br) 1.00-1.23(3H. br).1.08(6H, t F=7.2Hz), 2.79-2.96(311, br), FF 3.10-3.49(2H, br), 3.26(4H, N0 dq, J=5.2, 7.2Hz), 3.55(2H, 4.84(2H, 7.04(1H, d, 3=1.Hz), 7.07-7.14(2H, in), 2-14 00N N 3 7.15-7.24(3H, m), A ~N 7.28-7.37(3H, m), 7.37-7.43(11, m), 7.44-7.69(7H, 8.30(1H, d, 3=8.3Hz), 8.88-9.17(11, br) 1. 02-1.24(3. br) 1. 12(6H, t, F J=7.2Hz), 2.47-2.59(2H, m), 2.80-2.96(3H, br).

A 0- N 3.10-3.51(2H, br), 3.30(41, 2-15 N dq, J=5.7, 7.2Hz), 3.55(21, N N s),4.07-4.18(2H. m) 7.09(1.

d, 3=1.5Hz), 7.22-7.43(7, m) OH. 7.43-7.70(9, 8.28(11, a.

J=8.3Hz), 8.85-9.14(1l, br) 270 cl Table 21 UExample Structure NMR (8.3001Hz,CDC1) F 1.07(6H, t, J=7.2Hz), F l.32-1.71(SH, br), Cj 3 .10- 3 7 9(8H, M),3.54(2H, s), 2 6 C. 14.84(2H, 7.03-7.79(15H, N 0 8.28(31, d, H Ct% 9.04(H, brs).

00 8 217 0~ 4. 84(2H, 7. 03-7 .72 l 0 0 8.34(1H. d, 3=7.2Hz), 0.65-1.01(3H. br). 1.21(6H, t, F F 3=7.2Hz), 1.43-1.66{2H, br), I7 2.75-2.98(3H. br), o 30.53.41(2H.br). 3.51(2H, s).

0 0 4.21(4, q J=7.2Hz), 4.82(2H, 1 -9 2-18 N 0CHI 7.04{1H. br-s), 7.19(1. dd H 3 8.6Hz). 7.24-7.35(1.

a Ci m) 7.39(111. dd. 3=1.5, 7.5Hz).

CHN 7 .4 3 7 .69(7H, 8.18-8.31(1H, m.p. 106.8-109.4 br), 5.94-9.18(1H, br) 0.68-O.99(3H. br). 1.08(6H, t, 3j=7.lHz), 1.4-1.692H, br), F F 2.79-2.98(3H, br), F 3.063.42(2H. br), 3.26(4. dq, o 3=5.6, 7AHz). 3.55(2H1, s).

0 4.84(2H, 7.04(H11. d, 2WL9a oH, J=1.OHz). 7.11(2H,. br-t.

2-19 1 NI N J=5.6Hz). 7.15-7.24(3H, i).

0 N A 7 27 -7.36(3H, 7.37-7.43(lHs cM 3 in), 7.44-7.69(7H, in), 8.21-B.35(1H, br).

8.92-9.18(1H. br) 0.67-1.00(3H, br), 1.13(6H, t, F F 3=7.1Hz), 1.43-1.67(2H, br) F 2.48-2.59(2H, mn), 2.82-2.98(3H, br), 0 3.06-3.42(2H. bri. 3.30(4. dq, 22 0 0~ o J=5.6. 7.1Hz). 3.54(2H. s).

H I 4.07-4.17(2H, 7.09(111 d, c0 N31.42Hz), 7.22-7.42(7H, m), 7 43 -7.69(9H, m),8.2O-8.34(lH.

br). 8.89-9.14(1H. br) Table 22 Example structure

F

2-21 0 F

N

2-22 m.p. 130-131 NM (8,300rHz,CDC13.) 1.04(3H, t, J=7.2Hz), 2.84(3H, brs). 2.95(3H, brs), 3 .16-3.29(2H, m) 3.50(2H,

S),

3.64(11. dd, J=7.7, 3.91(114, dd, J=10.9, 4.64(1H, dd, J=10.9, 7.7Hz).

5.28-5.38(11, m), 7.00-7.71(15H. m) ,8.34 (1H, d, 9.15(IH, brs) 1.21(6H, t, 3=7.1Hz), 1.73-2.00(4H. m), 3.

2 2 -3.5 3.(4H, m) 3.51(2H, s), 4 .20(4H, q, J7.1HZ)) 4.83(2H.

7 .15-7.70(15H, m), 8 .33(1H, d, J8.9Hz). 9.84(11, brs).

1.21(6H, t, 3=7.1Hz), 1.35-1.70(6H. br), 3.0-3.76(4H, br), 3.51(2H, 4.20(4H, q, 3=7.1Hz).

4.82(2H, 7.03(1H, d, 3=2.0Hz), 7.12-7.68(14H,

M),

8.26(H, d, J=8.5Hz), 9. 06(lH, brs).

1.11(3H, t. 3=7.6Hz), 2.19(2H, q, 3=7.6Hz), 2.84(3H, brs), 2.95(3H, brs), 3.54(2H, s), 4.28(1. dd, 3c11.3. 4.9Hz), 4.41(11, dd, J=11.3, 5.25-5.33(1. 5.87(1l, d, 3=8.3Hz), 7.04-7.71(15, m), 8.

3 6(1H, d, J=8.5Hz). 9.14(IH, brs) 1.11(3H, t, J=7.5Hz), 2.1 9 2

H,

q, J=7.5Hz), 2.84(3H, brs), 2.95(3H, brs). 3.54(2. s).

4.29(11, dd, 3=11.3. 4.9Hz), 4.41(11, dd. 3=11.3, 5.26-5.33(11, 5.86(1H, d, 3=7.9Hz), 7.04-7.71(15H, m), 8.36(11. d, 3=8.7Hz), 9.14(1H, brs) 2-23 m.p. 118-120 2-24 2-25 1m.p. 95-98 1 1_ CICI rp :aoe .3 Examle Structure NMR (6.300MHzCDC13)

I

2.53(4W, 2.89(3H, brs), 2.96(3W, brs), 3.55(2H; s).

4.66(1W, dd, 3=10.9, 5.3Hz), 5.10(1H, t, 3=10.9Hz), 5.37(11, dd, J=10.9,5.3Hz), 7.07-7.69(15H, M) 8.35(.1, d.

3=8.7Hz). 9.17(1H, brs) 2-26 I m.p. 152-155 1 2-27 2-28 1.19(3W, t, J=7.2Hz), 2.70-3.01(6H. br), 3.41(2W, dq, 3=5.6, 7.2Hz), 3.60(2H, 5.32(2H, 6.18(1H, br-t. J=5.6Hz). 7.04(1K, a, 3=1.9Hz). 7.21-7.29(1H, m), 7.30-7.56(7. m), 7.56-7.66(4H, 7.69( 1, dd, 7.1Hz), 8.35(1H, d, 3=8.7Hz). 9.09(I, br-s) 1.04(3H, t, J=7.1Hz), 2.70-3.00(6W, br). 3.22(2H, dq, J=5.7, 7.1Hz), 3.53(2H, 3.57(2H, 5.13(2H, s), 5.43-5.54(1H, 7.08(1H, d.

3=1.9Hz), 7.21-7.43(6H. m), 7.44-7.66(6H, m), 7.69(1l, dd, 3=1.5. 7.2Hz), 8.34(H, d, J=8.6Hz), 9. br-s) 1.26-1.68(6H. m), 2.61-3.00(6H, m) 2.93-3.12(1. i), 3.58-4.01(18, m), 4.28-5.03(3. m), 7.09-8.32(17H, 9.14(1W, brs), 9.40-10.24(28, n) 1.10(6H, t, 3=7.3Hz), 3.06(6H, bra), 3.21-3.42(4H, i), 3.61(2H, 4.86(2H, a), 7.06-7.77(13W, 8.37(1W, d, =8.5Hz), 9.21(11, brs) 2-29 2-30 -0

F

0 NH N 0 0 NH C- 0 N

CR

ICHI

_I 273 M 11 1 '3 fl .L r LX Examlplel Structure NMR (6,300MHZ,CDC. 3 1. 23(6H, t, J=7.1Hz) 2.98(3H, brs) 3.05(3H, brs), 4.22(4H, g, 3=7.1Hz), 4.85(214, s), 7.11-7.75(11H, m) 8.35(1H, d, 9.21(11, brs) 2-31 N00C at, m.pv 106-110 1.24(6H, t, 3=7.2Hz), 2.61(2H, F F Nt, 3=7.1Hz), 2.86(3H, br.s), 2.94(3H, br.s), 3.46(2H, s).

1 4.07(2H, t, 3=7. 1Hz) 4.23(4H, 2-32 0 0 0 C, 00 J=7.2Hz), 7.08(1H, d, N J=1.9Hz), 7.23-7.68(14H, in), H N H8.36(1H, d, 3=8.6Hz), 9.15(IH, ON br.s) at 1.22(6H, t,3J=7.2Hz), 2.83(3H.

br.s), 2.94(3H, br.s).

0 t 3.51(2H, 4.21(4H, q, A o-trA.\ 3=7.2Hz), 4.83(2H, s), 2-33 0 N' 7.00-7.51(14H, 7.68(1H, lr c- 1 A at dd, 3=7.6, 1.5Hz), 8.37(IH, d, I N3=8.3Hz), 8.93(11, br.s) at m.p. 125-128 1.22(6H, t,3J=7.21z), 2.86(3H, Br Nbr.s), 2.95(3H, br.s), 0 A3.51(2H, 4.21(4H, q, 3=7.2Hz), 4.83(2H, s), 7.01(11, d, 3=2.2Hz), 2-34 N 0 C 7.19-7.53(13H, 7.68(11,

NN

H dd, 3=7.6, 1.5Hz), 8.40(1H, d, A N'H, 3rm8.3Hz), 9.O1(1H, br.s)

CH,

m.p. 124-128 F 1.96(3H, 2.84(3H, bra), 2.95(3H, brs), 3.54(2, s), 4.29(11, dd, J=11.6, 4.39(1, dd, J=11.6, 7.1Hz), 2-35 0 N NXNNH 5.23-5.33(1H, 5.90(1H, d, N 0 3=8.1Hz), 6.99-7.71(15H, m), n 8.36(1H, d, 3=8.5Hz), 9.14(1H, N a W brs)

OH,

Table 25 Eapestructure NMa 300HHZ,CDC1 3 0.92(3H1, t, 3=7.4HZ), CflF 1.56-1.68(2H,n), 2.14(2H1, t, F~ 3 =7.5Hz), 2.84(3H1, brs), N 2.95(3H, brs), 3.54(2H., s), 4.29(111, ad, J=11.4, 4.9Hz), o2-36 04.40(111, dd, 3=11.4. 7.1Hz), N C) o 5.23-5.33(111, in), 5.90(1H, d, 00 H 3=8.1Hz), 7,05(111, a, Cl 8.36(111, d, 3=8.5Hz), 9.15(111, It-)) 0 1.07(3H, t, J7.3Hz), 1.08(3H1, 0N t, 3=7.3Hz), 2.97(3H1, s), 2-3 N 0 N N 3.10 (3H1, s) 3. 18-3.31(4H, in), 2-373.59(2H1, 4.87(2H1, d, A A 0 0 NI0 3=4.1Hz), 6.38(1H, d, 03 =8.2Hz), 6.92-7.64(18H1, m), 7.83(111, d, 3=6.8Hz) N1. 21(6H,t, 3=7. 1HZ), 2 .96(3H, 3.07(31,6s), 3.55(2H1, d, N 3=7.1Hz), 4.20(21,q 0 0 0 321z,41(2H, q, 2-3 A 0 CF J =7.1Hz), 4.B2and4.89(2H, each d, 3=11. 2Hz) 6. 36 (1H, d, N Cit 3=8.2Hz), 6.93-7.59(16H, in), 01) 7.83(.1, d, 3=6.8Hz) 2.73-3.00(6H1, br), 3.52(21, F s 3.72(61, 4.82(21, s), A 7.03(111, d, 3=1.9Hz), A 7 .1 6 7 .36(6H, m) ,7.40(1H, dd, 0 0-01, 3=1.5, 7.5Hz), 7.45-7.65(6H, 2-9N 0 0 2-392 m 7.69(11, dd. AH H I C 7.2Hz), 8.35(111. d, 3=8.7Hz), CN 9.17(111, br-s) m~p.108.8-112.4 F 1.21(6H1, t, 3=7.1Hz), FF 1.31-1.60(6H1, m), N 0 1.67-1.82(2H, mn), A 0 2.40-2.57(111, M,m) 2.88(3H,.

2-40 0 0 bra), 2.94(3H1, bra). 3.53(2H,.

N NK 4.14(4H1, q, 3=7.1'Hz), H? 4.48(2H1, 7.09(111, a, A 0 N 3=1.8Hz), 7.21-7.72(911, in), Cli, 8.37(1H, d, 38.4Hz), 9.16(1H, in.P. 110-111 brs).

Table 26 Example Structure 2-41 m.p. 108-110 2-42 m.p. 121-124 NM" (8.300MHz.CDCl 3 0.95-1.19(6H, 1.21(6H, t, 1.60-1.80(4H, m), 2.00-2.18(1, 2.88(3H, brs).. 2.95(3H, brs). 3.52(2H, 4.14(4H, g, 3=9.5Hz).

4.50(2H, 7.09(1H, d, 3=2.7Hz), 7.19-7.73(9H, i), 8.38(11, a, 3=11.3Hz), 9.18(1H, bra).

l.22(6H, t, J=7.2Hz). 2.84(3.

br.s), 2.94(3H, br.s), 3.51(2H, 4.21(4H, q, 3=7.2Hz), 4.83(2H, a), 7 .01(1Hd, J=1.9Hz), 7.20(1H, dd,3=8.7. 1.9Hz).

7 .26-7.51(12H. 7.68(11 ad, J=7.5, 1.5Hz), 6.40(1H, d, 3=8.7Hz), 9.00(1H, br.s) 1.21(6H, t, J=7.2Hz), 2.57(3H.

2.75(30H br.s). 2.94(3H, br.s). 3.50(2H, 4.20(4H.

g, 3=7.2Hz). 4.82(2H, s), 7 .DO(IH, d, J=1.9Hz). 7.8(1H.

dd, J=8.6, 1.9Hz), 7.26-7.59(11H, 7.70(1H, dd. 3=7.6, 1.5Hz), 7.95(1H, d, 3=8.3Hz), 8.35(11, d.

3=8.6Hz), 9.13(11. br.s) 1.07(6H, t, J=7.3Hz), 2.7 6 3

H,

2.86(3H, 3.21-3.30(4, 3.57(2H 4.83(2H, s), 6.82(14. d, 3=8.3Hz), 6.98-7.45(16. 8.24(14, ad. 3=7.8, 1.8Hz), 8.44(1H. d, 3=8.5Hz). 10.4(1H, brs) 1.22(6H, t, 3=7.1Hz). 2.75(3H, 2.82(3H, 3.54(2H, a), 4.21(4H.q, J=7.lHz), 4.

83 2

H,

6.82(1H, d, 3=7.6Hz).

7.05(11, d, 3=2.0Hz), 7.09-7.46(13H, 8.24(1i, dd, J=7.8, 1.8Hz). 8.42(11 d, 3=8.5Hz). 10.4(1H, brs) 2-43 2-44 2-45 I __I Table 27 Example Structure NMR (&,300MH z,CDC13) 122(6Ht, J7.2Hz) 2.90(3H, I I br.s). 2.97(3. br.s), 1 I 3.52(2, 4.21(4H, q.

3=7.2Hz). 4.83(2H,

S),

2-46 0 00 0 7. 05(1H, d, 31.9Hz) 7.20(11.

T 0 N 0 dd.38.7, 1.9Hz), 0% 7. 29-7. 7(13H, m) 8. 33 IH, d, A0 0J =8.7Hz)1 9.27(1W br.s) 00y .2l(6H, t,3.7.2Hz) 2.44(3H, 0 Ns), 2.77(311 br.s). 2.91(3H, N

A

0 br.s). 3.50(2H, 4.20(4H, 2-4 Ao0 A\ q. 3=7.2Hz), 4.82(2H1, s).

o 7.01(1H. a, 3=2.2Hz) 7.19(1H.

N N N 0 0 K dd,3=8.7, 2.2Hz), _r 7.30-7.59(12, 8.35(18, d, I o3=8.7Hz), 9.08(1H, br.s) 1.21(6H, t, J=7.1Hz) 2.44(3H, F F 2.80(3H, br.s). 2.94(3H, N br.s). 3.50(2H, 4.20(4H, q, J=7.1Hz), 4.82(2H, s), 2-48 o 0N:0 0 7.02(1. a, J=2.2Hz), N N N 7.16-7.30(8H m).

SD7.56-7.63(58, m) 8.35(11 d, HICC J=8.7Hz), 9.14(IH. br.s) 0, m.D. 105-108 F 2.65(3H, 2.86(3R, brs).

F F .343( H 2.95(3H, brs). 3.61(2H, s), 4.23-4.30(2H1. m), N 4 7 1-4.79(111,m).4.98((1H,d.

2-49 A 0 =7.1Hz). 7.09(1. d, A 0 ;rho 3=1.9Hz). 7.18-7.71(14, m), H c8 3 8.37(1H, d, 3=8.7Hz). 9.16(18, 0 N' brs)

CF

1.19(,.t.3 7.1Hz), 2.8 6 3

H,

F trs), 2.95(3H, brs). 3.52(2H, N Fs), 3.89(111, dd, J=9.1, 6.OHz), 4.02-4.19(2H, m).

4.34(1. dd, J=10.9. A- N50t 4.58(IH, dd. 3=10.9. 9.1Hz).

A 0 0 7.06(11, d. 3=2.3Hz), S=7.18-7.71(14H7 m)8.36(IH, db 0 386f) 9.17(lH, brs) NMR (b,300MHZ,CDC1) 1.12-1.18(3H. n), 2.21-2.46(2H, i), 2.64-3.49(9H. m), 3.55-3.58(2H4, 4.45-5.29(2,

M),

6.11-6.19(lH,

M),

7 .12-7.70(15H,

M),

8.33-8.38(1, 9.17(IH, brs) Conformer 1.24(6H, t, 1. 50-1.64(2H, m) 2.25-2.36 (2.

2.

7 7 -3.02(6H, br), 3.54(2H, 3.99-4.08(2H, m), 4-16-4.29(4H, 7.10(1H, .d, 3=1.9Hz), 7.24-7.43(7H. m).

7 .44-7.57(2H, m) 7.59-7 64 4

H,

7.68(1H, dd, J=1.5. 7.2Hz), 8.36(11, d, J=8.7Hz), 9.16(11.

S)

1.21(6H, t. 3=7.0Hz), 2.82(3H.

br.s), 2.95(3Hbr.s). 3.50(2H, 3.88(3H. 4.21(4H, g, 3=7.0Hz), 4.82(2H. 6.87(1H.

d, 3=2.6Hz), 6.99(11, 2.6Hz), 7.03(11. d. J=I.BHz), 7.18(11. dd, J=8.5, 1.8Hz), 7.29-7.69(.OH, 8.35(11, a, 3=8.8Hz), 9.17(1H. br.s) 1.21(6H, t, J=7.OHz). 2.81( 3

H.

br.s), 2.94(3H, br.s).

3.51(2H, 4.20(4H, q, 3=7.0Hz), 4.83(2H, s), 7.04(1H, d, J2.2HZ). 7 1 9 ddJ=8.

4 2.2Hz).

7.30-7.66(12H, 8.33(IH, d, 9.29(1H, br.s) 1.20(6H. t, 3=7.1Hz), 2.11(3H, 2.88(3. bra). 3.04(3H, brs), 3.48(2Hs), 4.19(4H, q, J=7.1Hz), 4.81(2H, 7.04(lH, d. 3=2.0Hz). 7.12(11, dd, 3=2.0Hz, 7.24-7.50(101. 7.60(2H, d, 3=8.1Hz). 8.10(11, d, 9.06(1H, bra).

Table 29 Example Structure NMR (8,300MHzCDC1a) 2.81(3H, brs), 2.93(3H, brs), 1 F 3.52(2H,S), 4.45-4.60(4. i), F 4.88(2H, 7.02(1H, d, 1 J=2.0Hz). 7.19(IH, dd, o-56 0 CF\ J=2.OHZ, 3=8.7Hz).

In N 07.23-7.64(12H, 7.68(1H, Id, 3=2.0Hz, 3=8.1Hz).

00 A Or.. 0 8.34(11. a, J=8.1Hz), 9.10(1H, 0M, brs).

1.21(6H. t, J=7.1Hz), 2.95(3H.

0 I FF F brs), 3.01(3, brs). 3.52(2H, 0

F

0~ 4.21(4H, g, 3=7.1Hz), 4.83(2H, 1.10(1H, S), F o c 7.14-7.63(12H. 7.75((1H, N N V0 d, 3=6.6Hz), 8.22(1H, d.

HI Or =8.7Hz), 9.34(11, brs).

c, mp 1165-119.5 1.23(6H.t, 37 .1Hz). 2.85(6H, F F Nbr-s), 3.55(2H, 4.22(4H, F 00 A 0 Q, 3t7.1H), 4.83(2H, s), 7.03((1H, d, 37.6Hz), A-8 t o o\ 0 .24-7.74(13H, 8.36(1H, d, N 0 J=12.2Hz), 9.45(11, br-B).

HCH

AICN 0 y mp 119-121 1.22(6H, t, J=7.1Hz), 2.87(3H, F F Ns), 2.96(3H, 3.51(2H, s), 4.22(4H,qc.3J7.Hz), 4.85( 2

H,

0 7.06(11. brs), A-5 0 0\ 7.25-7.68(14H, 7.77(1H, d, 2-59 0 0 N 0 0 =7.1Hz).

H Ct N 0 N 1.22(6H, t, 3=7.1Hz), F 2.86(3, brs). 2.95(3H. s), 0 3.50(2B. 4.22(4. q, A C1 3=7.1Hz), 4.85(2H1,

S)

2-60 0 A% 7.00(11, d, 3=1.5Hz).

N Ki 7.20-7.66(13H, 7.73(1, 3CH, dd, 3=1.5Hz, 3=7.1Hz), 7.97(1H, brs).

CH,

Table Example 'Structure toei 300MHz, CDC1,) 1.21(6H. t, 3=7.2HZ), 2.88(3H!.

F F brs). 2.97(3H1. bra), 3.52(2H1.

F0s), 4.20(4H1, g. 3=7.2Hz), 2-61 0 0=2.2Hz). 7.18-7.72(13H!, m), Iral Nl 8.33(11!, d, 3=8.4Hz). -9.33(11!, -0 brs).

00 nip 131-133 lfl 1.21(6H1, t. 3=7.1Hz). 2.87(3H!, F brs). 2.96(3H!, bra). 3.52(2H,.

0 Ns), 4.21(41. q. 3=7.1Hz), -4.83(2H,. 7.07(111, d, 2-62 NH 8.32(11!. d, 3=8.4Hz), 9.32(11!, 0 I br-a).

nip 120-125 N~O, 1.22(1,t 3=7.2Hz), 2,83(3H!, F F Nbra), 2.94(3H, bra), 3.48(2H,.

F 4.23(4H,. q, 3=7.21Hz), N 04.94(2H,. 6.98(111, d, 2-63 A 1 A- 0* o- 0 4 =1.9Hz), 7.12-7.76(1011, m), N N0 8.30(111, d. 3=8.3Hz). 8.38(111.

A 0 N'HC dd,, J=2.6Hz, 3=8.9Hz), 9.08B(11, OI bra), 9.22(1H. d. 3=2.6Hz).

1.21(6H!, t, 3=7.2Hz). 2.83(3H,.

F F Nbrs), 2.94(3H1. bra). 3.48(2H,.

F N11a), 3.49(11!, bra), 3.71(111.

A

0 bra). 4.20(4H1, g, 3=7.2Hz), 2-64

A

0 A 4.88(2H,. 6.83(111, dd.

N

1 0 0 05 =3.0Hz, 7.03(11!. d, H oil 3=1.9Hz),' 7.11-7.72(101. in).

0 N-10 7.83(111. d, 3=3.1Hz), 8.25(111, F F N1.21(6H1, t. 3=7.2112), 2.83(3H1, F NIbra). 2.93(3H, bra), 3.49(21, N N 0 4.21(4H. gl. 3=7.2Hz).

04.93(21, 7.03(111, d, 2-65 0 0 0 c' 3=1.9Hz), 7.13-7.73(12H1, mn).

N 0 8.33(11!, d, 3=8.6Hz), 8.47(111.

A r o NM 60, 3=3.8Hz). 9.17(11!, bra).

mp 149-155 Table 31 Example Structure I NMR (6,300xHz,CDC 3 2-66 2-67 1.23(6H, t, J=7.2Hz), 2.88(3H, 2.97(3, 3.61(2H, s), 4.23(4H, q, J-7.2Hz), 4.85(2H, 7.03(1, a, J=7.lHz).

7.23-7.68(12, 7.74(11, 3d, J=1.1Hz, 3=7.5Hz).

7.84(1K, brs).

1,23(6H,t,J7.2Hz), 2.88(3K, 2.963H, 3.62(2H, s), 4.23(4H. q, 3=7.2Hz), 4.85(2H, 7.09(11, d, 3=7.5Hz), 7.24-7.68(12H,

M),

7.74-7.80(2H, i).

1.22(6H, tTJ=7.2Hz) 2.26(3H, 2.84(3. bra), 2.95(3H, brs), 3.48(2H.

S),

4.10-4 61(4H, m) 4 .88 (2H, s) 6.99-7.73(14H, m) 8. 43(1H, d, 3=8.3Hz), 9.18(1H, brs).

1. 21(6H, t. 3=7 2Hz), 2. 32 (3H, 2.81(3H, bra), 2.93(3H, brs), 3.51(2H, 4.20(4H, q, 3=7.2Hz), 4.81(2H, a).

7.01-7.74(14H, m) 8.36(H, d, J=8.3Hz), 9.19(1H, br-a).

1.21(6Htt, 3=7.2Hz), 2.33(3H.

2.82(3, bra), 2.94(3H, bra), 3.51(2H, 4.20(4H, q, 3=7.2Hz), 4.81(2H, a), 7 .01-7.74(14H, 8.35(1H, 3=8.3Hz), 9.19(1, bra).

2-68

F

FF F

H

2 0 N N 0 0 0 N H C 0ot 2-69 2-70 I I T'able 3 Example Structure MM (6,30OHz CDC1,).

I

1.24(6H, t, 3=7.2Hz), 2.84(3H, F F br-s), 2.95(3H, brs), 3.44(2H, NII 0 4.12-4.35(4H, 4.94(2H. 7.O0(1H, d, 2-71 A N=2.2Hz), 7.05-7.73(13H, m), 8.31(1. d, 3=8.3Hz), 9.19(1H, 03 bra).

F 1.22(6H, t,;3=7.1Hz), 2.81(3H.

F F br), 2.94(3H, bra). 3.51(2H, 4.21(4H, q. J=7.lHz), 4.80(2H, 7.03(1H, a, 0 2-72 A 3=2.2Hz), 7.14-7.64(12. i), S A 0 0 a 7.70(11, dd, J=1.6Hz, 3= CI7.2Hz), 8.36(11, d, N,12215 J=8.6Hz), 9.19(1H, brs).

al, mp 12.2-25.0 a 1.21(6H, t, J=7.2Hz) 2.80(3H, F brs), 2.94(3H,. bra), 3.50(2H, 4.20(4H, q, 7=7.2Hz), 0 4.80(2H, 7.02(1H, d0, 2-73 A J=2.3Hz), 7.18-7.71(13H, m), A 0 0 0 C 8.36(1H, d, 3=8.3Hz), 9.18(11,

H

bra).

6 mp132.0-134.4 1.16(3H, t, 3=7. OHz). 1.18(3H, F t,3=7.2Hz), 2.82(3H, brs), N 2.93(3H,brs). 3.04(114, d, A J=16.5Hz), 3.20(H. d, 7 0 3=16.5Hz), 3.46(2H, a).

4.04-4.20(4H, i), N'A 0 0 0 C 4.75(1Hd=11.4H2).

H 4 .82(1H.dJ=11.4Hz), §.98(IH.

N H;CN 0 0, 3=2'.2Hz), 7.11-7.72(14H, at 8.34(14, d, J=8.OHz), 9.17(11, bra).

1.22(6H, t, J=7.1IHz) .2.8 4 3

H,

F bra); 2.94(3H, bra), 3.44(2H, 3.74(3H, 4.22(4H, q, .3=7.1Hz), 4.81(2H, a), S0 6.84-7.7(14H 8.32( d, AJ=8.7Hz), 9.18(IH, brs).

1 T1 Example structure f NMR (5,36oMHz,CDC13 F 1.21(6H, t,3J7.1HZ). 2.82(3H1, F F moo bra), 2.94(3H4, bra,., 3.51.2H, I as), 3.77(3H. 4.20(4H4, q, 0 3=7.1Hz),- 4.81(2H, a), 2-76 0 N6.83-6.91(3H4, mn), 7.04(114, a, N 0 0 o) oi 3=1.9Hz), 7.18-7.71(104, mn), HN 8 35 (11, d, 3=8. 3Hz) 9. 19 (114, FSCNN bra).

FGM. 1.21(6H. t, J7.lHz), 2.80(3H4, F F brs), 2.93(3H1, bra). 3.51(2H1, I as), 3.79(3H, 4.20(4H4, q, N 0 =7.1Hz). 4.80(2H4, S) 2-77 o N 6.84(214, at, J=5.6Hz, 0 a 0 0 3 =3.4Hz), 7.03(1W d N ~J3=.9Hz). 7.19-7.71(11H, mn), R2C 0n 8. 36 (1H, d. J=8. 7Hz) 9.18 (1H, bra).

F F ~1.21(6H, t,3J7.2HZ). 2.82(3H., F bra), 2.940H14 bra), 3.52(2H4, 0 4.21(4H4, q, 3=7.2Hz),

A

0 A 4.83(2H4, 7.05(114, a), HN 7.61-7-84(7H4, mn), 8.34(1H, d, F I0 H =8.3Hz), 9.40(114, brs)

F

m.p. 11I 1 1.20(6H,t,3J7.2HZ), 2.86(3H4, FF Nbra), 3.06(3H4, bra), 3.50(2H4, N 0 4.20(4H4, q, 3=7.2Hz), 0I1\ 4.82(2H4, 7.06(1H, s), 2-79 c, N 0] C] cK. 7.15(114, ad, 3=2.1, 8.3Hz), N VH 7. 28 63(12H4, mn), 8. 14 d, A N~ 0 3=5.3Hz), 9.25(114, bra) 135-138 1. 21 (6H,t,J=7.-OHz), 2.83 (3H, FF Nbra), 3.00(34, bra), 3.51(24, N 0 4.21(4H4, q, 3=7.0Hz), A A- 4.82(2H4, 7.05(114, a, 2-80 F N 0 0 0 ,J22z,7.19(114, dd, 3=2.2, N N K-o 8.4Hz), 7.25-7.65(12H4, m), H 8.27(114, d, 3=8.4Hz) 9 .28(114, bra) rYLp. 12B&130 283 Table 34 o Example Structure NMR (b,300MHz,CDC 3 1.24(6H, t, 3=7.2Hz), 2.44(3H, F F 2.61(3H, t, 3=7.1Hz).

F 0 2.86(3, brs). 2.95(3, brs), 3.46(2H, 4.07(2H, t, 2-81 N J7.1Hz), 4.23(4H, q, J=7.2HZ), 4.82(2H, 7.07-7.63(14H. m), InI l HAa8.37(11, d, 3=8.7Hz). 9.12(1H, 00 bra) 005 n I I 1.21(6H, t, 3=7.1Hz), 1.45(311, F F t, 3=7.2Hz), 2.81(31H, bra), o FF 2.95(3, bra), 3.50(2H. s), l N4.11(2H, g. J=7.2Hz), 4.21(4H, q, 3=7.1Hz). 4.82(2H, s), 2-82 I s 6.86(1H, d. 3=2.6Hz), 6.97(1H, N a dd, 3=2.6, 8.7Hz), 7.03(11. d.

1 A 3=1.9Hz). 7.18(11, dd. 3=1.9, Os 8.7HZ), 7.28-7.30(5. mi), 7.56-7.67(5H, 8.36(11. d, 3=8.7Hz), 9.17(11, brs) 1.21(6. t, 3=7.2Hz), 1.28(6H, d, J=6.OHz), 2.81(3H, bra).

2.95(3H, brs), 4.21(4H. q.

0t 3=7.2Hz), 4.64(11, sept, =6.0Hz), 4.82(2H1 s),6.85(lH, 2-83 0% d, 3=2.2Hz), 6.96(1H, dd, 3=2.6, 2N 0 8.7Hz), 7.03(1H, d, J=2.2Hz).

00 ~lib 7.18(I, dd, J8.7, 1.9Hz), Os% 7.28-7.30(5H, m),7.56-7.

6 6 8.36(1. d, 3=8.3Hz), 9.16(11, bra) 1.24(6H, t, 3=7.2Hz), 2.61(2H, F F Nt, 3=7.1Hz), 2.89(3H, bra), F 0 2.94(3H. brs). 3.47(2H, a), N-N 4.08(2. t, 3=7.1Hz). 4.24(4, 2-84

A

0 A0 g. J=7.2Hz). 7.11-7.39(7. m), N Os 7.61-7.83(7. 8.34(11, d, F 3 J=8.7Hz), 9.36(1. brs)

F

F F 1.20(6H, t, J=7.2Hz). 2.81(3H, F brs), 3.02(3, bra), 3.49(2H, N? 3.78(3, 4.20(4H, CH, 0 A ti7 .2H) 4 .81( 2 H, 7.02(11 2.85 0 d, J1.Hz), 7.07(1. a, N 0 0 WC, J=8.3Hz), 7.15(11, dd, 3=2.3, 0 V' 8.7Hz), 7.24-7.30(6H, m), oH 7.41-7.60(5H, 8.22(1, d, m.p. 107-109 38.7z), 9.05(11, bra) cl Table 0) Example structure NMR (b,300MHzCDC1,) 1.21(6H, t, J7.2HZ), 2.48(3H, F F Ns), 2.69(3H, brs), 2.91(3H,

F

D Nbrs), 3.50(2H, 4.21(4H, q, 0 J7.2Hz), 4.82(2H, s), 2-86 0 0 0 o 6. 99(1H, d, 3=2. 2Hz) 7. 20(1H, 2-8 N dd, 3=1.5, 8.3Hz), K C 03 7.28-7.41(81. m).

O 0 7.57-7.64(4H, 8.18(1H, d.

CH, y3=8.6Hz), 8.81(IH, brs) rmp. 125-129 1. 23(6H, t, J7.2Hz) 3.00(3H, brs), 3.03(3H, brs), 3.58(2H.

s 0 4.22(4H. q, 3=7.2Hz), 4.85(2H, s. 7.18(lH, d, 2-87 F 0 3=1.9Hz), 7.28-7.33(6H, m), 0 O r N t 779(1, d, 3=7.9Hz), 7.92(11, 1A H d, 3=7.9Hz), 7.99(1H, s).

8.35(1H, d, 3=8.3Hz) 9.46(1H,

S)

1.21(6H, t,3J=7.2Hz) 2.33(3H.

2.76(3H, brs), 2.93(3H, 0. brs), 3.50(2H, 4.21(4H, q.

6.99(11, d, 3=1.2Hz).

2-88 1' C C 7.14-7.51(13H,m) 7.65(1H, d.

I J=7.6Hz), 8.34(1l, d, 3=8.6Hz), 8.78(1l, brs) m.p. 129-131 1.24(6H, t, J=7.2Hz) 1.29(3H, t, J=7.6Hz), 2.92(2H, g, 0=7.6Hz), 3.03(6H, brs).

v 01 3.57(2H, 4.23(4H. q, 2-89 N 0 03=7.2Hz), 4.85(2H, s), F013 7.l8(1H, d, 3=2.3Hz), 7.27-7.33(6H, m), F 07.51-7.60(3H, 8.40(11, d, mp.B-82 J=8.2Hz), 9.51(1, brs) 1. 21(6H, t, J=7. 1Hz) 1.22 (3H t, 3=6.9Hz). 2.64(H, g, 0 J=6.9Hz), 2.75(3H, bra), 2.93(3H, bra), 3.50(2H, s).

0 CH3\ 0 2-90 0 N0c 4.21(4, q, 3=7.1Hz), 4.82(2H, 6.99(1, d, J=1.8Hz).

A o l -~7.17-7.66(14H, m) 8.30(1H, d, I0 J=8.3Hz), 8.76(11, brs)

A

(saq 'tLO 'HT)8L6 '(ZHE-9=Y' 'HI)6Z''9 '(ZHL*LL'P p HT)99L 0 'Ht)9tL '(wu HZ!)TIO'L-OV .L 0 I SN- S6-Z '(wl 'HI)969T6*9.'SH)S' '(ZHT'L=C 'b 'Ht)Cr't

N-

'HZ)LS*E '(sslq 'HC)01E '(sz7q 'HEOWE '(zjflvL=C '4 'H9)EV'T 'HI)V6 '(ZHEVS= P 'HT)1EP9 g (S 'HT)C9.L 'HZ)ZS*L '2 a N NP '('H9)EErL-9Z-L '(ZH61C~ 'P 0 'HT)SV'L *AS 'xfl9iV '(Zwv-L-r tvs t'*0s 6- 'b 'V)z't 'HZ)LS-E

QO

'(ZHg'g=r 'ides K0 '(szq 'Hg)CO'c '(2Hg'9Cr '4 'H9)6Z7T '(ZHV*L=C 'H9)tvt"- 'HI)SV'6 '(2HI?9=C 'P 'HT)9V-9 p '(zH6sL=C 'P MTCL'L '(ZH6'LC 0 P 'HT)'E9'L 'HT)SS'L 'pN

N

'(in 'H9)TE'&-SZ*L '.(zH9'T~C 0 N E- 'P 'HT)S1?L 'HT)EV' 0; A 2 'HT)ST'S 'HZ)S9'k '(zZL=C 'b 'uP)EZ'( S 'nz)gS'c '(ssrq0 'HE)V0S* '(s-IQ 'HE)66*Z '(sN 'HC)ZT*Z '(ZHZVL=r 'H9)tZ'TE (SJxQ 'HT)L9goLLo,~ 'p H'I)19 'm 'HT)IVL-4VL 0 'P 'HT)TO'L 0 N NE 'gZ)zw"V '(ZHT'L=C 'b 'HP)11D' 'HZ)OS*C '(ss:q 'Ht)W6Z \O 0 8 :91 '(zHT*L=C 'ides 'H!)69'Z 0 '(ssQ 'HE)9L'Z '(ZHT*L=r '4 'H9)Tr'T '4 (szrq 'HT)LS'9 '(2H9-9=C 'P 'Ht)6V9 (ZH'L 'P 'Ht)L9"L 0-l 00 'Am 'xrT)ES'L-BV'L '(zllt>

HK

'6"1Cr 'PP 'HT)6T"L '(ZHrr"Cr 0 0 'P 'HT)96"9 'HT)tt"S CH -6' 'HI)OT'S '.HZ)8rV'(zHtrL=rN 'b 'HP)Or''J 'Hr)61rE *(saq0 'HC)6S'Z '(Sz7Q 'nc)TL'Z

NI*

'nE)EttZ '(ZjfVL=C '4 'H9)TZ'1 exn4Dt'ZHWfClS eK Tdumr3 (CT~a'zf~oo9E aWNe 286 (N Table 37 Example structure NMR (6,300MHzCDC13) :l.21(6H, t, 3=7.1Hz22.7 5 3

H

F F brs), 3.02(3H, brs). 3.55(2H1, 09 4.20(4K, q, 3=7.1Hz), 2-96 I 0 c, 3=8.3Hz), 7.15-7.68(14H, m), 0 0 0 y 8.07(11, dd, J=1.3, 7.7Hz) t HC-.N o InI 00 l c~ 1.22(6H, t, 3=7. lHz), 2.83(3H, F F brs), 2.86(3H, brs), 3.53(2H, 4.21(4H, J=7.1Hz), oI-k%4.83(2H, 6.85(11, a, 2-97 0;O\ J=7.7Hz), 7.07(1, d, 0 J=2.OHz), 7.20-7.52(12H, m), 0 8.25(11, dd, J=1.8, 7.9Hz), 8.41(H, d, 013 I 10.48(11, brs) F F 0.65(6H, t, J=7.4Hz), 1.69(4H, F q, 3=7.4Hz), 2.81(3H, brs), 2.94(3, brs), 3.50(2H. s), 9 04.30(2H, 7.02(11, d, 0 IM J=1.8Hz), 7.18-7.62(13H, m), 2-98 0 CH 7.70(111, d, 3=7.3Hz), 8.35(11, 0 N,0% 3=8.5Hz), 9.15(1H, brs) 1.21(6H, t, J=7.lHz). 2.87(6H, F N brs) 3.53(2H, 4.21(4H, q, F A =7.1Hz), 4.83(2H, s), d A6.92(1Hd, 7.6z), 7.08(11, 29 d, 3=2.1Hz), 7.20-7.48(10, 7.63(2H, d, 3=8.7Hz), A J, o 'rCH. 8.23(11, dd, J=1.7, 7.9Hz).

c8.35(11, d, 10.38(1, brs) 0.85-0.93(4H, 2.78(3H, F F brs), 2.93(3H, brs), 3.52(2H, 4.16(2H, 7.04(lH, d, 3=2.1Hz), 7.17-7.61(13H, m), a -7.70(1, dd, J=1.5, 7.2Hz), 2-100 8.35(1H,. d, =9.0Hz), 9.15(1, brs)

I

*1*able Excample Structure NMR (6.300MHZ .CDC1 3 2.79(3H, brs), 2.94(31, brs).

F F 3.45(2H1, 4.31(2H, t, p 1 3=7.6Hz), 4.62(2H,. d, o 3=7.6Hz), 6.96(111, d, 2-101 I =2.0Hz), 7.15-7.69(19H1, mn), N 8.30(111. d, 3=8.5Hz), 9.15(1H, I 1 ,.CH 2 brs) 1CH 1 F F 1.62-1.76(4H. in), F 1.82-1.99(4H, mn), 2.78(31, N A brs), 2.93(3H1, brs), 3.44(2H1, 2-102 03=2.0Hz), 7.09-7.26(6H, mn), N 0 7.35-7.72(8H1, mn), 8.34(111, d, -HC. -N 3r=8.5Hz), 9.15(111, brs) -F F 2.40(1H, t,.35.7HZ). 2.42(111, F t, 3=6.3Hz), 3.53(2H,. s), A 2.80(3H1, brs), 2.93(3H1, brs), A0 0 OH 3.82(2H1, ad, J=6.3, 11.4Hz), 2-103 3.96(2H1. ad, J=5.7. 11.4Hz).

N ar OH 4.58(2H1, 7.01(111, d, H 3=1.8Hz), 7.14-7.71(14H, in), A 0 N' 8.29(111, d, J=8.4Hz), 9.05(1H, brs) F F 1.98(611, 2.83(3H1, brs).

F 2.93(3H1, brs), 3.49(2H1, s), FI 4.40(4H, 4.44(2H1, s), A o 0 Ii 7.00(111, d, 3=2.2Hz), 7.15(1H, 2-104 A ad, 3=2.2. 8.4Hz), 0 0 H 'rLH 0~ 7.22-7.65(12H, mn), 7.70(111.

H~1 a H F d, 3=1.9, 7.0Hz). 8.32(111. d, 0 N 333=8.4Hz). 9.13(111, brs) F 1.23(6H,t, 37.1Hz). 2.8 3 3

H,

F F b-rs), 2.94(3H1, brs), 3.51(21, 0 4.22(4H1,g.

J=7.lHz),4.82( 2 H, s), 2-10 A0 6.94-7.04(31, in).

A0 0 0 %H 7. 16-~7.71 (10H,f) 34 (1H, d, TN N.

3 3=8.5Hz), 9.17(111, brs) m1 p.98.8-1 03 3 288 Table 3 9 E. xample structure iMR (baOoNHz,CDC3-j) 0 4.20(4H, q, 3=7.1Hz).

o2-106 N7.25-7.71 (11H, mn), 8. 35 (1W. d, tfl~~ CN N 9.17(1W, brs) 00 tC) F 1.25(6H, t, 3:7.lHZ)., 2.75(3H, o F brs), 2.92(311, brs), 3.7B(2H, O N 4.22(4H, q. 3=7.1Hz), N 0 4.85(2H, 6.98(1W. s), 2-107 y 7.28-7.72(13H, mn), 8.71(111.

N 00 cM, 9.52(IH, brs) H

K

0 W' ICNi F 22(6H,t, J=7. 2Hz), 2 .13 (3H, FF 2.85(3H, brs), 2.93(3H1, CHI brs), 3.50(2H, s),

C

2-108 0 N7 6.78 (11, d, 3=5.1Hfz) 7 .05 (1H, 0. o o H d, 3=2.2Hz), 7.15(lH, d, H F 3=5.2Hz), 7.16-7.64(8H1, m), NH 0NCii, 7.69(1W, dd, 3=1.5, t-3Hz), cB. 33(1H. d, J8B.SHz)., 9 .16(1H, brs) 1.22(6H, t, 3=7.2Hz). 2.44(3H, F F3 2.84(3H, brs). 2.94(3H, :r brs). 3.52(2H, 4.20(4H, g, Ns/ 0 3=7.2Hz), 4.781(2H. 6.58(1W.1 o dd, J=1.2, 3.5Hz), 6.76(1W, d, 2-109 N 3=3.5Hz), 7.04(1W, d. 3=2.0Hz), -I 0 0 a 7 N 0 04,F 7.20(1W, dd, J=2.1, 8.6Hz), N 7.37-7.62(7H, in), 7.68C1H, dd, WkN'CF C't 3=1.4, 7.6Hz), 8.33(1W. d, 04% mp.1a4.6-IoB.3 3=8.4Hz). 9.17(1K 1 brs) F ~1.22(6H, t,3J7.1Wiz), 2.85(3H, F F brs), 2.94(3H, brs), 3,46(2H, (N 4.23(4H, g, 3=7.1Hz).

N0 4.97(2H, 7.00(1W. d, 2-110 0 0 =2.2Hz), 7.13-7.16(111, in), 7 N 00a cii, 7.36(1W, d, 3=3.3Hz), H 7.38-7.71(8W, in), 7.75(1W, d, N 0 N" CH 3=3.3Hz), 8.31(1W. d, k' In..Il.S- 124 7 3=8.5Hz). 9.16(1W. brs) c~ Table o tucueNxn (&300MHz. CD1 3 Example Structure F 0.97(6H, d, J=7.2Hz), 1.21(6H, CC) IIF ~F it, J=7.2Hz), 2.45(IH. sep.

CH, 3=7.2Hz), 2.88(3H, brs), 2.94(2H, brs). 3.52(2H, s).

2-111 4.15(4H, q. 3=7.2Hz) 4.50(2H, 0 CH, 7.09(11, d, 3=2.3Hz).

H C 7.20-7.72(9H. 8.34(1, d.

00 OH1 J=8.3Hz), 9.15(11. brs).

CHI mp 96-98 0.90(3H, t. 3=7.2Hz), 0.92(3H, o F F t. 3=6.5Hz), 0.95-1.10(11, m).

CHI 1.21(3. t, 3=7.2Hz).

0 1.48-1.62(1H, m).2.O5-2.16(lH.

2-.2 0- o# 2.88(3H, bra). 2.94(3H.

0 CH, brs). 3.52(2H 4.14(4H. q, N HOJ=7.2Hz) 4.51(2. 7.09(111, 'N H, i J=1.9Hz). 7.21-7.72(9, m), OH, mp 100-104.5 8.36(11. d. 38.31z), 9.16(11, bra).

0.83(6H, d, J=6.4Hz), 1.21(6l.

F t. 3=7.2Hz). 1.51-1.65(11. m).

NHs 0 1.88(2H, d, 3=6.4Hz),'2.88( 3

H.

bra), 2.94(3H, bra), 3.53(2H.

2-113 0 4.15(4H. q, 3=7.2Hz), 0 4.52(2H, 7.08(11, d.

N H 3-2.3HZ). 7.22-7.71(9, I 0 8.37(1. d. 3=8.3HZ). 9.16(1.

CH, mp 106-109.5 brs).

F 0.88(3H, t, J=7.2Hz).

F F H, 1.09-1.31(2H. 1.21(6H. t.

3=7.2Hz), 1.79-1.93(2H, m), 2.89(3H. bra). 2.94(3. bra).

2-114 3.53(2H. 4.15(4H, q, A A=7.2Hz). 4.49(2H. 7.09(1.

H brs), 7.21-7.74(9H, i).

N 0 OH, 8.37(11, d, 3=8.3Hz), 9.15(1.

CH, mp 98-99.5 brs).

0.83(3H. t. 3=7.5Hz), 1.21(6H.

F F t, 3=7.2Hz). 1.96(2. q, 3=7.5Hz). 2.88(3H, bra).

2.94(3H, bra). 3.53(2. s).

2-115 A N 4.16(4H, q, 3=7.2Hz). 4.50(2H, 0 Ao 0 0 7.08(lH. J= 1. 9H z).

C 7.21-7.74(9H, 8.36(11, d, NN 0 H 3=8.7Hz). 9.15(11, bra).

OH, mp 86.5-90.0 Table 41 [Exa-ple .Structure 2-116 2-117 nip. 76. 9-82- C 0-63,J =7.2Hz)4.9H.) 7081, d,06=2.36(H. 7. 1.1(6H. t, 1=.2(61 t.83=71Hz. 2.67(2m).

d,8837.H r) 2.9(3, brs), 4.10-4.041 4.47(24H, a), J7.2(1H, 4,49=2.Hz .0l d,35-7.68(7.2in).7.70(19H, d), J.1.411z. d.,7(11.H) d.J".4HZ).

9rs.1(1,ba 1.21(6H, t, 3=7.2Hz). 2.69(32H, 2.9531 br. 3.56(2s).

a.104.23(4H, 4.=72H.

4.70(2.10(H 7,1(1. 6.67(H 7.21.d.3=.2z) 7.28-7.70(87H, 8.36(111, d, 3=.8Hz). 9.1(1, rs 0.87(39H, t, 3=7.2Hz)-O.89(3H, t.s) 2=.8.9(H 100-1.((2Hin) 1.20(61.(H t. 3=1Hz).

1.38-1.53(2), UT.lH 2.82231, ml, .85(311.4H,ra). 2.(311 7.22-7.70(98H, in). 8.35(11,6., 3=8.6Hz), 9.15(111, bra) 2-118 2-119 moi. 72.3-78. 6

J.

C Example 3 2-(2-{3-Ethoxy-4-[(4'-trifluoromethylbiphenyl-2e carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid ci diethyl ester 0 a) 3-Ethoxy-4-nitrobenzoic acid methyl ester 00 0 0 o ^CH 3 0 CH, 0 0 0 02N

O

2

N

OH OEt To a suspension of sodium hydride (60% mineral oil: 1.20g) in dimethylformamide (50 mL) was added 3-hydroxy-4nitrobenzoic acid methyl ester (4.93 g) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes.

After addition of ethyl iodide (4 .4 the solution was stirred at 60 0 C overnight, cooled down to room temperature, poured into saturated aqueous ammonium chloride, and extracted with ethyl 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 yellow solid.

b) 3-Ethoxy-4-nitrobenzoic acid chloride 0 0 0 0 OH N C 0,N 0 2 N OEt OEt OEt 292 0 0 N 3-Ethoxy-4-nitrobenzoic acid chloride was obtained in a Ssimilar manner to Example 1 f) and Example 1 d) from the 3-ethoxy-4-nitrobenzoic acid methyl ester obtained in Example 3 a).

O 5 c) 2'-Diazo-3-ethoxy-4-nitroacetophenone 0 0 0 "i •C oCHN V0 ON CHN O Et OEt 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 2 to give the title compound (1.80 g) as a yellow solid.

d) 3 -Ethoxy-4-nitrophenylacetic acid ethyl ester

CHN

2 0N A 0 ON A OEt OEt A solution of silver benzoate (270 mg) in triethylamine (2.7 ml) was added dropwise in 10 divided doses to a solution Sof the 2'-diazo-3-ethoxy-4-nitroacetophenone (1.80 g) obtained in Example 3 c) in ethanol (25 mL) under reflux. The c 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 00 with 10% aqueous sodium carbonate, water and saturated brine.

tf The organic layer was dried over sodium sulfate and purified D 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 OEt OEt The 3 -ethoxy-4-nitrophenylacetic acid ethyl 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-2carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid diethyl ester

CFI

HN 0 0 S Et N X000 H DEt The 4-amino-3-ethoxyphenylacetic acid ethyl ester obtained in Example 3 e) and the 2-hydroxymethyl-2- 294 phenylmalonic acid diethyl ester obtained in Example 1-2 a) were O subjected to reactions similar to those in Examples 1 e) 1 f) en and 1 g) to give the title compound (0.159 g) (see Table 42).

ci o 5 Example 3-2 C {3-Hydroxy-4-[(4' -trifluoromethylbiphenyl- 2 00 carbonyl) amino phenyl }acetic acid 2,2-bisethylcarbamoyl-2ci n phenylethyl ester

CF

3 N O O N0 O N NHEt

CF

0 N HEt H OH {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.

obtained were shown in Tables 42 to The compounds thus 1CI *1 aDie L Eample TStructure NME (8,300MnzCDC1) I 1.19(6H, t, J=7.1Hz), 1.20(3H, t, 3=7.1Hz).

3.49(2H. 3.77(2H, q, 3=7.1Hz). 4.18(4H, q, 3=7.1Hz). 4.83(2H, s), 6.59(1H, d, 6.75(lH, dd, J=1.5.8.2Hz).

7.25-7.33(5H, 7.44(11, dd, J=1.5. 7.2Hz.), 7.49-7.66(6H, m), 7.70-7.76(1H, 7.80(1H, dd, J=1.5, 7.2Hz), 8.35(1H, d, J=B.Hz) 1.05(6H, t, 3=7.2Hz), 3.23(4H, dq, J=7.2, 7.2z), 3.48(2H, 4.83(2H, s), 6.48(1H, d, J=7.9Hz).

6.55(1H, d, 3=7.9, 1.9Hz), 6.77(11, d, 3=1.5Hz), 7.17-7.86(151, m) ,8.58(1H,s) 1.05(6H, t, 3=7.2Hz), 3.23(4H, dg,3J=7.2, 7.

2 Hz), 3.53(2H, 3.55(3H, s), 4.83(2H, 6.60(1H, s), 6.73(1, d, J=7.9Hz), 7.10-7.66(15H, n), 7.85(1H, dd, 37.5, 5.33(11, d, 3=7.9Hz) i.19(6H, t, 3=6.9Hz), 3.50(SH, s), 4.17(4H q. 3=6.9Hz), 4.83(2K. 6.58(1l, a), 6.75(11. d, 3=6.9Hz), 7.26-7.65(131, m), 7.85(11, d, 3=7.3Hz), 8.31(1H, d. =8.1Hz) n.p. 112-114 0.84(6H, t, J=7.2Hz), 1.43(4H, tz, J=7.2. 7.2Hz), 3.16(4H, 3.52(2H1, 3.55(3H, 4.83(2H, s), 6.60(IH, br.s), 6.72(111.

dd, 3=8.3, 7.12-7.66(15, m), 7.84(1H, dd, J=7.9, 1.9Hz), 8.33(11, d, 3=7.9Hz) U aD.Le Example Structure NMR (b,30MHZCDC1) 1 3-6 3-7 3-8 1.13(6H. t, 3=7.2Hz), 2.55(2H, t, J8. OHz), 3.30(4H, dq, 3=72.

7.2Hz), 3.53(2H, 3.57(3H, 4.12(2H, t, 3=8.0Hz), 6.67(1H, br.s), 6.82(1K, ad.

3=8.3, 1.9Hz), 7.26-7.66(15H, 7.84(1H, dd,3J=7.9, 1.9Hz).

8.33(1H, d 1.05(6H, t, 37.2Hz), 1.24(3H, t, t7.Hz), 17-3.29(4H, m), 3.52(2, 3.83(2H1, g 7.Hz), 4.82(2, 6.60(H. d, 6.69-6.76(H.in), 7.04-7.

3 4(2H.

7.15-7.22(2H,

M).

7n25-7.34(3H. 7.41-7.47(K.) .4-766(K, m) 7.73(.s br-s), 7.8(11. I, 8.371.

d, J-83Hz) 1.10(6H, t, 3=7.2Hz), 1.24(3H, t, 3=7.2Hz), 2.49-2.59(2, m), 3.31(4H, dq, J=5.3, 7.2Hz), 3.52(2H, 3.87(2H, q, J=7.Hz), 4.07-4.17(2H. m), 6.68(11, d, 3=1.5Hz).

6.78-6 8(1, 7.23-7.37(5H.

7.41-7.46(1l, n), 7.48-7.66(8H, 7.73(7, s.

7.76-7.82(H, 8.37(IH, d, J=8.3Hz9 1.10(6H, t, J=6.OHz), 1.1(61, t, J=7.2Hz), 3.48(2, s), 7.19(4H, 3, J=7.2Hz), 4.36(1.

sept, 3=6.1Hz). 4.82(2H, s).

6.62(1H, d, 3=1.5Hz), 6.70-6.75(11, 7.27-7.32(5H, 7.41-7.46(3H, m), 7.49-7. 67(6Hm), 7.72-7.82(2H.

8.39(11. d, 3=8.3Hz) 1.05(6H, t, J=72Hz), 1.13(6H, d, J=6. lHz) 3.23 (4H, dg, J=5.6, 7.2Hz), 3.52(2, 4.40(lH, sept, J=6lHz), 4.82(2H, s), 6.62(lH, d, 6.67-6.75(H, 7.10(2H, br-t, J=56H), 7.16-7.23(2H.

7.24-7.35(3H, 7.44(IH, dd, J=1.5, 7.6Hz), 7. 50-7.70(6R1, m) ,7.71-7.82(2H, 8.40(IH, d, J=8.3Hz) 3-9.

3-10 I I A A T4 ab~e alf Example Structure NMR (5,30 MHz,CDC1)

Y

3-11

F

F- I F 1.13(6H, t, J7.2Hz). 1.13(6H, d. 3=6.1Hz), 2,48-2.60(2H1, 3.31(4H, dg. 3-5.7, 7.2Hz).

3.52(2H, 4.07-4.17(2H m), 4.43(IH. sept, J=6.lHz), 6.69(111, d, J=1.5Hz), 6.79(1, dd, 3=1.5, 8.3Hz).

7.23-7.37(5H, 7. 41-7 .46( 111 7.48-7.68(8. i), 7.72-7.82(2. 8.40(11, d, 3=8.3Hz) 0.90(3H, t,3J=7.4HZ). 1.05(6H, t, 3=7.3Hz), 1.53-1.69(2H, m), 3.16-3.30( 41,m) 3.53(2H, s), 3.75(2H, t, 3=6.7Hz) 4.82(2H, 6.58-6.74(2H, i), 7.02-7.78(161 8.36(18, d.

Z=8.2Hz) 1.04(6H. t, J=7.2Hz), 3.

2 3( 4

H.

dq, J=7.2, 7.2Hz), 3.52(2.

4.82-4.86(4H, m), 6.70-7.79(16, 7.71(11, br.s), 7.78(11, dd, J=7.1, 1.9Hz), 8.40(1W, d. J=8.3Hz) 3-12 3-13 1.19(6H, t, 3=7.1Hz).3.49(2H, 4.17(4H, q. 3=7.1Hz), 4.78(2H, 4.83(2H, a), 6.70(1H, d. J=1.9z), 6.78(1H, 0 CH3dd, 3=8.3, 0 i 7.21-7.57(12, 7.70(H, F% br.s), 7.77(1H, dd, J=7.2, 1.9Hz), 8.38(11, d, 3=8.3Wz) 3-14 3-15 O-,CH3 1.20(6H, t, J=7.2Hz), 3.47(2H, 4.19(4H, q, 3=7.2Hz), 4.82(2. 6.29(11, d, 3=7.9Hz), 6.57(18, dd, J=7.9, 1.9Hz), 6.79(1H, d, J=1.9Hz), 7.18(11, br.s), 7.28-7.74(118, 7.86(11.

dd. J=7.9, 1.5Hz), 8.39(1, s)

I

Table Example Structure F F

F

N.

A

3-16 0o o o 0 011o

,C

7 e NMR 300MHZ,CDC13) 1.17(6H, t, J=7.1Hz), 3.54(2H, 3.72(3H, s), 4.16(4H, q, J=7.1Hz), 4.83(2H, s), 6.72-6.80(3H, m), 7.29-7.66(12H, m), 8.14(1H, dd, 3=1.3, 7.7Hz)

I

Example 4 2-(3-Dimethylamino- 4 -trifluoromethylbiphenyl- 2 carbonyl)aminol phenyl)acetic acid 2,2-bisethylcarbamoyl-2phenylethyl ester a) 2-( 3 -Bromo-4-nitrophenyl)malonic acid tert-butyl ester methyl ester

F

0 2

N

Br CCOOtBu \N COOMe 0 2 N 1 Br Sodium hydride mineral oil; 0.985 g) was suspended in dimethylformamide (20 mL) and a solution of tert-butyl methyl malonate (4.29 g) in dimethylformamide (5 mL) was added dropwise thereto under ice-cooling. After foam generation is stopped, a solution of 2 -bromo-4-fluoro-l-nitrobenzene (2.71 g) in dimethylformamide (5 mL) was added dropwise thereto at the same temperature, and the mixture was further stirred at ^c 60 0 C for 3 hours, and then concentrated. The residue was neutralized with IN hydrochloric acid and extracted with ethyl Sacetate. The extract was washed with saturated brine, dried over sodium sulfate and concentrated. The residue was purified o 5 by column chromatography on silica gel with ethyl 01 acetate:hexane=l: 4 to 1:5 to give the title compound (7.54 g) 00 as an oil.

o b) 3 -Bromo-4-nitrophenyl)acetic acid methyl ester 0 C eCOOMe COOtBu N jCOOMe ON 0 2 N X 02N Br Br 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 N VCOOMe 0NCOOMe 0 2 NAC 02N Br

/N

The 3 -bromo-4-nitrophenyl)acetic acid methyl ester (0.320 g) obtained in Example 4 b) was dissolved in c tetrahydrofuran (10 mL). To this solution were added C) triethylamine 237 g) and dimethylamine (2M tetrahydrofuran 0.58 mL). and stirred overnight while heating. The reaction C 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.

00 d) (4-Amino-3-dimethylaminophenyl)acetic acid methyl ester ci COOMe HN COOMe o 4 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-2phenylethyl ester

CF

3 H0 Hz COOMe N 0 0 NHEt S H 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 1 f) and 1 g) to give the title compound (0.058 g) (See Table 46).

302 Cq Examples 4-2 to 4-8 SCompounds 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.

<0 00 cn ci 303 (N Table 46

U

U Example Structure NMR (6,300MHz,CDC13 1.04(6H, t, 3=7.2Hz), F F 2.26(6H, 3.23(4H, i), (N F 3.51(2, 4.83(2H. s), I 6.86-7.80(15H, m), 8.40(1H, d, 3=8.7Hz).

0 0 H CH, 8.45(11, brs).

'No N N' 3 oc 00

CNCL

(N 1.05(6H, t, 3=7.3Hz), F F 1.49(6H, br.s), 2.48(4H, F br.s), 3.24(4H, dl 0 J=7.3, 7.3H), 3.53(2H, 0 N 4.84(2H. 6.93(21.

4-2 0 0 H CN i 7.20-7.70(15H, m), N N o 8.40(1H, d, 3=9.2Hz).

H N CH 8.54(1, br.s) 1.04(6H. t, 3=7.3Hz), F F 1.76(4H, i), F 0 2.59(4H, t, J=6.2Hz), 3.23(4H, dq, 3=7.3, 0 0 ON-- 7.3Hz), 3.51(2H, 4-3 0 0 H 4.83(2H, 4.82(2H, m), N O [r 7.12-7.63(14H, m), H dd, =7.3, 0 1.4Hz), 8.18(111, br.s).

8.30(111, d, 3=8.1Hz) F F 1.20(6H, t, 3=7.1Hz), F1.48(6H, br.s), 2.47(4, br.s), 3.49(2H.9S), 0 A4.19(4H, q, J=7.1Hz), 4.83(2H. rNi N O H3 6.92-7.72(15H, m), N 8.39(1. d. 3=8.3Hz), C9 8.56(1H, br.s) 1.20(6H, t, 3=7.2Hz), F F N1.74(41, 2.57(4H, m).

I 3.48(2H, 4.19(4H, q, 3=7.2Hz), 4.82(2H, S), 0 0 o$ 6.90(2H, i), 7.30-7.63(12H, m).

N' N \.CH 7.74(111, dd, 3=7.2, H 1.5Hz), 8.20(1H, br.s), 8.29(11, d, 3=8.7Hz) I Table 47 [Example Structure 4-6 NMR (,300HHZ,CDC1) 1.20(6H, t, 3=7.1Hz), 2.24(6H, 3.48(2H, s), 4..19(4H, q, 3=7.1Hz), 4.82(2H, s).

6.88-6.98(2H, n), 7.29(5H, brs),7.43( 1H, d, 3=7.2Hz), 7.48-7.60(2H, m), 7.62(4H, 7.77(3H, d, 3=7.5Hz), 8.39(1H, d, 3=8.3Hz), 8.47(11, brs).

1.21(6H, t, 3=7.0Hz), 2.38-2.47(4H,

M),

3.51(2H, s), 3.53-3.60(4H, m), 4.20(4H, 3=7.0Hz).

4.84(2, 6.93(.1, s), 7.00(3H, ad, 7.4Hz), 7.29-7.35(H, m), 7.47-7.68(7H, i), 7.73(3H, dd, 3=1.8, 7.4HZ), 8.42-8.51(2H. m) 0.67(6H, t, 1.21(6H, t, 3=7.2Hz), 2.64(4H, q, 3=7.Hz),.

3.49(2H, 4.21(4H, q, 3=7.2Hz), 4.83(2H, s), 6.90-7.01(2H, i), 7.28-7.35(5S, m), 7.42-7.65(7H,

M),

7.69(11, ad, 3=1.5, 7.2Hz), 8.41(1, d, 3=8.3H1), 8.85(-1, br-s) 4-7 4-8 C H, 305 Example 2-{2-(2-{2-methyl-3-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyllacetoxy)ethyl]-2-phenylmalonic acid diethyl ester o 5 a) 2'-Diazo-3-nitro-2-methylacetophenone 00 I 0 2N?" OH 0 2 N2 0) 0 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 0

CHN

2 O 2

NN

0 2 N 2 O 02N OEt 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 0 GEt 22N OH 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 306 0 SOBn 0 Br BnO OEt P n1$OEt 0 0 0 Sodium hydride (406 mg) was dissolved in dimethylformamide (20 mL) and the solution was cooled to 0°C.

00 STo this solution was added phenylmalonic acid diethyl ester n 5 (2.0 and the mixture was stirred at room temperature for o 30 minutes. Bromoethyl benzyl ether (2.0 g) was further added thereto, stirred at 60 0 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 BnO OEt HO OEt OEt 0 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}-2phenylmalonic acid diethyl ester 02 0n o C N OH HO OEt 0 0 0 '4 The 2-methyl-3-nitrophenylacetic acid (307 mg) obtained V in Example 5 4-dimethylaminopyridine (217 mg) and the o 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-methyi-3-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyl}acetoxy))ehyll-2-phenylmalonic acid diethyl ester

CF

3 0 ON 0 OEt 0 OEt Q N j 0 OEt The 2-{2-[2-(2-methyl-3-nitrophenyl)acetoxy]ethyl}-2phenylmalonic acid diethyl ester (345 mg) obtained in Example 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 48 to 51.

308 Cl Table 48 o Example Structure N1R (8,300NHz,CDC13 1.23(6H, t, 3=7.0Hz), Cfl 1.70(3H, 2.61(2H, t, Fl 3=7.OHz), 3.50(2H. 4.07(2H, t, 3=7.0Hz).

"10 4.21(4H, q, 3=7.0Hz).

6.84(11. br. 6.98(11, d, OHS0I c, 0=7.7Hz). 7.13-7.71(15H, 00 K.3 7.80(1H, d, 3=7.0Hz) IF F 1.17(6H, t, J=7.1Hz), o F 3.50(2H, 4.14(4H, q, O N 3=7.1Hz). 4.83(2H, s).

6.83(1. 6.91(11. d, 5-2 0 0 0 =7.5Hz), 6.99(IH. br.s), 5-ON C7.16-7.81(15H, m) H 0 F F 1.23(6H, t, J=7.2Hz), 2.62(2H, t, 3=7.2Hz), N3.41(2H, 4.13(2, t, 0 3=7.2Hz). 4.20(4H, c, 5-3 J=7.2Hz), 7.05-7.79(18H, H 0 N m) m.p. 88-91 1.10(6H, t, 3=7.2Hz), F F 2.53-2.61(2H, 3.28(4H, F dq,3J=5.3,7.2Hz). 3.54(2H.

Is), 4.07-4.17(2H, m), 5-4 0 0 0 6.95-7.10(3H, m), 7.14-7.36(7H, m).

N 7.40-7.46(1H. m), 0 CH, 7.46-7.62(6H, m), el-" 7.64-7.71(2H, 7.77(11, ad, 3=1.5. 0.85(6H, t, 3=7.2Hz), 1.49(4H. tq. 3=7.2, 7.2Hz).

2.54-2.63(2H. m), 3.16-3.25(4H. 3.53(2H, 4.08-4.17(2H, m), 5-50 0 0 6.96-7.01(1H m).

N 0 7.03-7.10(2H, m), H WN-c 7.15-7.36(7H, m).

0CH3 7.40-7.46(1 m), CF, 7.47-7.62(6H. i), 7.65-7.71(2H. 7.77(1, dd. J=1.5, cI Table 49 o Example Structure NMR (b,300M z,CDC1) 1.24(6H, t, J=7.4Hz), F 1.68(3H, 2.65(2H. t, Fc J=7.3Hz), 3.50(2H, s), 4.09(2H, t, J=7.3Hz), 5-6 0, DU 4.22(4H, q, 3=7.4Hz), o Nr0 6.81(1, br.s), H o 6.92-7.83(16H, m) 00 1.23(6H, t, 3=7.4Hz), F F 2.20(3H, 2.63(2H, t, I I F 3.47(2H. S), o N4.08(2H, t, 3=7.0Hz), 5-7 o 0

C

3 0 4.21(4H, 3=7.4Hz), 0 6.94(1H, s), Q CHl 7.07-7.81(16H. i) 03 1.11(6H, d, 3=6.4Hz), F F 1.13(6H, d, J=6.8Hz), 2.49-2.58(2H, 3.53(2H, 3.98-4.15(4H, m), 00 6.96-7.01(11, m), 5-8 N7.03-7.16(3H, m), H -IJ~ 7.17-7.37(8H,

M),

0 H' 7.40-7.61(5H, i), F C CH3 7.64-7.71(2H, m),7.77(lH, dd, J=1.5, 7.6Hz) l.11(6H, t. 3=7.0Hz), F F 1.72(3H, 2.52(2H, t,

F

J=7.9Hz), 3.29(4H, dq, I 1 J=7.0, 7.0Hz), 3.57(2H1, s), 5-9 0 04.08(2H,'t. J=7.9z), N 6.85(11, br.s), N 'NI 6.99-7.81(18H, m) AH, o 0.98(6H, t, 3=7.1Hz), 1.53(2H, 1.79(3H, s).

p F F 1.95(2H, 3.09(4H, dq, J=7.1, 7.lHz), 3.64(2H, s), 4.06(2, 3=5.7Hz), 5-10 7.03-7.62( m), 0sa 8.02(H, br.s) I 310 cl Table

U

Example structure NMR (b,300MHz,CDC1) 0.86(6H, t, 3=7.1Hz), Fn 1.50(4H, tq, J=7.1.,7.1Hz), 2.53(2H, t, 3=7.9Hz), 3.21(4H, 3.57(2H, s), 5-11 0 4.08(2H, t, .W7.9Hz), oJ: 6.85(11, br.s), 7.00.(1H, d.

A 0 J=7.5Hz), 7.14-7.80(17H, 00

CH)

Cl 11.11(H, t, 3=7.2Hz), o f 2.53(2H, t, 3=7.9Hz), 0 3.22(3, 3.29(4, dq.

Cl 3=7.2, 7.2Hz), 3.55(2H, s), 5-12 A 4.09(2H, t, 3=7.9Hz), N~ NN~~N 6.95(H, dd,3J=7.5, H OJHCH 7.04-7.64(16H,

M),

A HC 0 H 7.74(11, dd, 3=7.5. 1.5Hz) 8.34(11. d, J=8.3, 1.1Hz) 1.23(6H, t, 3=7.1Hz), F F 2.61(2H, t, J=7.2Hz),

F

3.22(3H, 3.49(21 s), 4.08(2H, t, 3=7.2Hz), o a A 4.21(4H, q, 3=7.1Hz), 5-13 N 0\ 6.93(1H, dd, 3=7.6, H 0 CH, 7.28-7.75(14H, m), A C 'D 0 7.73(11. dd, J=7.6, 1.5Hz) 8.33(1, ad, J=8.3, u.p. 78-81 F F 1.11(6H, t. 3=7.4Hz), F 1.15(3H, t, 3=7.2Hz), 2.52(2H, t, 3=7.5Hz), 0 3.29(6H, 3.54(2H, s), 5-14

A

1 4.09(2H, t, N t\ 6.95(11, dd, J=7.9, 1.1Hz) 0 N C 7.10(11, dd, 7.9Hz),

N

1 'C8, 7.24-7.73(16H, i), a, 58.36(11, d, 3=5.3Hz) 1.15(30. t. 3=7.2Hz). 1.23(6H, P F t, 3=7.2Hz), 2.61(2. t, F J.7.2Hz). 3.29(2H. q, J7.2HZ).

3.49(2H 4.07(2H, t.

A 15-0 0 A 0 3=7.2Hz), 4.21(4H, q, J7.2Hz), 5-1 N 6.9411H, 66, J-7.5. H 0P j 0 7.08(11, 66. 3=7.9 7.9Hz).

0 7 .30-7.73(14H, 8.34(1H, dd, CH, J3=7.9, rt T able 51 Example Structure J MR (6,300MHZ.CDC3 1.05(6H, d, J=6.4Hz), 1.23(6H, t, J=7.2Hz).

F F 2.62(2H, t. J=7.2Hz).

F 3.51(2H 3.85(114 sep 1 N=6.4Hz). 4.10(2H, t, 51 3=7.2Hz), 4.20(4H. q.

5-16 3=7.2Hz), 6.95(1, dd, 0\ 3=7.9, 1.5Hz). 7. 07( 1. dd.

H- U 01CH, C 0 0 3=7.9, 7.9Hz).

0% CH,' 7.30-7.61(12H, m).

7.68(11. dd. 3=7.9, 7.75(1IH br.s), 8.28(1H.

d, J=7.9, 1.23(6H, t, J=7.1Hz), F F 2.61(2H, t, J=7.1Hz).

F 3.71(3H. 3.75(2H, s), 4.07(2H, t, J=7.1Hz).

1 0 04.22(4H. q, J=7.1Hz).

5-17 6.94(1H, d, J=7.6Hz).

N 0 7.29-7.62(13, i).

H 0 F 0 7.72(1H, dd. J=1.4. 7.6Hz).

0 0 *-OA 3 8.47(1. d, 3=8.3Hz), 10.25(1H, brs) 1.13(3H, t, J=7.2Hz).

F F 1.23(6H. t, 3=7.1Hz), F 2.30(3, 2.61(2H, t, I UM I 3=7.1Hz) 3.25(2H, q,

A

0 A 0 3=7.2Hz), 3.44(2H, s).

5-18 -I 4.07(2H, t, 3=7.1Hz).

HN 0 0 c 4.21(14, q, 3=7.1Hz), \C 6.75(11, s), CM, 7.30-7.69(14H, n), 8.19(1H, brs) 312 C Example 6 O) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amno]benzoic acid 2-[9-(2,,2-trifluoroethylcarbamoyl)-9H-fluoren- 9-yl]ethyl ester a) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]benzoic Sacid ethyl ester

CF

3 CO~COOEt COOEt o00

N

H

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' -trifluoromethylbiphenyl-2-carboxylic acid (1.00 g) in a similar manner to Example 1 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)aino]benzoic acid

CF

3

CF

3 0 N COOEt

COOH

IH H- V H

C

N The 4- 4 -trifluoromethylbiphenyl-2- Scarbonyl)amino]benzoic acid ethyl ester (0.700 g) obtained in M Example 6 a) was subjected to reactions similar to Example 1 f) to give the title compound (0.680 g) as a white solid.

O 5 c) 9-[2-(Tert-butyldimethylsilanyloxy)ethyll- 9 H-fluoren- 9-carboxylic acid (22,22-trifluoroethyl)amide 00 o c 0 TBSO NH

O

CF

NH

CF

3 9H-Fluorene-9-carboxylic acid (2,2,2trifluoroethyl) 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

H

b 0 In o o) NH

NH

o NH

SKCF

00 CF I The 9-[2-(Tert-butyldimethylsilanyloxy)ethyl]-9Ho 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:l 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-9yl]ethyl ester O CF3 COOH HO 0 In o\ oo I H

NH

0 CF 00

CF

IH 0

NH

The 4-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]benzoic 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 1-2 c) and 1-2 The compounds thus obtained were shown in Tables 52 to 56.

(N Table 52 Example Structure NIR (b,300Mz,CDCa) F 2.98(2H, t, 3=6.8Hz).

F F 3.63-3.71(2H, 3.81(2H.

t, 3=6.8Hz), 5.27(1l, br), 0 7.00(1, brs), 7.12(2H, m), 6 o 0 7.30-7.84(181,

M).

N N

NH-

N H

F

00

F

2.45-2.58(2H,

M),

F F F 4.10-4.18(1K. 4.21(2H, 0 3=7.5Hz), 7.02(1H, brs).

0 7.14-7.88(20H, m).

-0 Ne 0

H

3.01(2H, t, 3=6.6Hz), 3.60-3.74(2,, 3.86(2H, N 3=6.6Hz). 5.27(18H, n), 7.20-7.61(18H, 7.75(2H, 6-3 H 0 d, 3=6.6Hz). 7.97(1l, brs), N N0 N F 8.52(11, d, 3=8.4Hz).

0 0 I F

F

3.56(2H, t, 3=5.2Hz), F 4.06(2H, t, 3=5.2Hz), F F 5.52(1H, br), 7.08(1H, brs), 7.15-7.98(21H, i).

N 0 6-4 A 0,N

N

1 N HN 3.42-3.54(2H, 3.55(2H, 4.26(2H, t, 3=6.6Hz), F 5.52(H, br), 7.06(H, brs), 7.18-7.88(21H, m).

cTable 53 l Txample5 Structure NMR (6.300MHZCDCls) F 2.31-2,42(11, m), F F 2.80-2.93(1H, i), 3.73-3.89(2H1. m), 0 4.16-4.26(11, m), 0-6 0 o 4.32-4.43(2H, 5.62(1.

6-6NH br), 7.09((1H. brs), NN 7.26-8.01(19, m).

00 i H

F

FF

2.15-2.29(2. 3.34(2H1, F FF t, 3=7.9Hz), 4.01-4.18(2H, 4.40(2H, t, 3=6.2Hz).

0 N 6.15(11, br), 7.08(11, brs), 0 A7.18-7.9817, 7.92(1l, 6-7 A d, 3=8.4Hz).

A N H NH

F

F 2.88(2H, t, J=8.3Hz), F F 3.83-3.93(2H, 4.23(2H, t, 3=8.3Hz), 5.90(1, t, 0 J=6.4Hz), 7.01(1H. brs), 6-8 A0 0 P 7.16-7.86(22H1, Ne 0 N I H F

F

F 2.12-2.29(1, in), F F 2.56-2.68(1H, i), 3.70-3.80(3H, n), 0 4.09-4.29(2H. 5.41(11, 6-9 A' 0br), 7.05(1H, brs), 7.12-7.78(20H, 7.86(1K, N d, 3=7.5Hz).

H

F

2.16-2.30(2H, m), F'FF 2.62-2.72(21, 3.61(1K.

t, 3=7.5Hz), 3.71-3.99(4H, 4.12-4.37(4H, i), 6-10 Nt"< F 5.67(11, br). 7.05(1, brs), A0 F 7.15-7.91(17. m).

I rrhlo 54 s

-F

Example Structure I

I.

6-11

N

H

F F

F

6-12

F

F F I N 0 ci CI K o 0 0 N

N

H

F

NMR (6,300OHz,CDC- 3 3.49(2H, t, 3=6.9Hz), 4.09-4.29(2. 4.56(2H, t, 3=6.9Hz), 6.34(11, br).

7.08(1H, brs), 7.12-8.00(18H, n).

2.39-2.50(11, m), 2.93-3.05(1H, i), 3.78-4.06(2H, i), 4.20-4.41(2K, 4.77(1H, d, 3=6.4Hz, 3=9.6Hz), 5.42(1, 11, t, 3=6.4Hz), 7.07(11, brs), 7.19-7.88(15H, m).

2.19-2.30(11,

M),

2.62-2.13(11, m), 3.79-3.2(2H, m), 4.20-4.40(3H, -5.80(1H, t, 3=6.4Hz), 7.06(1R, brs).

7.16-7.92(16 m).

1.22(61, t, 3=7.1Hz).

2.77(211, t, 3=6.9Hz).

4.21(41, g, 3=7.1Hz), 4.30(21, t, J=6.9Hz), 7.06(1H, brs), 7.19-7.88(17H, m) 1.23(6H, t, 3=7.1Hz), 1.64(3H, 2.77(2H, t, 3=6.9Hz), 4.21(4H, q, 3=7.1Hz), 4.29(2H, t, 3=6.9Hz), 6.93(11. brs), 7.20-8.24(16H, m) 6-13

NH

F

6-14 6-15 I rr~^ e: -I- au~le 55 Example Structure NMR (6,300MHz,CDC-,) 1 2P, j=7.lnn j 1.23(3H, t, 3=7.1Hz), 2.76(2H, t, J=6.9Hz), 4.20(2H, g, 3=7.1Hz), 4.21(2H, q, 3=7.1Hz), 4.29(2H, t, J=6.9Hz), 6.95-7.91(17H, m) 6-16 6-17 6-18 1.22(6H, t, J=7.lHz), 2.77(2H, t, 3=6.9Hz), 4.20(4H, q, 3=7.1Hz), 4.31(2H, t, 3=6.9Hz), 6.93(2H, d, 3=8.8Hz), 7.26-8.13(13H, 7.92(2H, d, 3=8.8Hz) 1.22(6H, t, J=7.1Hz), 2.76(2H, t, J=6.9Hz), 4.20(4H, q, 3=7.1Hz), 4.30(2H, t, 3=6.9Hz), 6.85(2H, d, J=8.8Hz), 7.21-7.81(13H, 7.88(2H, d, 3=8.8Hz), 8.21(11, dd, J=7.6, 1.3) 1.14{6H. t, 3=7.2Hz).

2.63-2.71(2H, 3.31(4H, dq, 3=5.6, 7.2Hz), 4.29-4.38(21, i), 7.15-7.20(11, m), 7.23-7.38(7H, m), 7.41-7.47(1H, m), 7.49-7.63(4. m), 7.64-7.75(4H, 7.81(1.

dd, 3=1.5, 7.86-7.93(2H, m) 6-19 F F

F

'N0 0 0N 00F CA

C

1.14(6H, t, J=7.lz), 2.65-2.74(2, 3.31(4H.

dq, 3=5.7, 7.1Hz), 4.33-4.43(2H, 7.08(11, d, 3=8.3Hz), 7.27-7.44(6H, 7.47-7.61(5H, m).

7.63-7.72(3H, 7.90(11, dd, J=1.9, 8.6Hz). 8.07(1H, d, 3=1.9Hz), 8.23(11, ad, 7.9Hz) 6-20 I I 320 0 c en ci 0o 00 Table 56 Example Structure 6-21 NMR (8,300reiz,CDC1) 1.14(6H, t, 3=7.2Hz), 2.64-2.73(2H,

M),

3.32(4H, dq, 0=5.6, 7.2Hz), 4.3l-4.41(2H 6.91-6.98(21, i), 7.26-7.36(5H, i), 7.41(1H, dd, J=1.1, 7.5Hz), 7.47-7.59(3H.

7.60-7.71(5H, i), 7 .94-8.0l(2H,

M),

8.11(1, ad, J=1.1.

1.13(6H, t, 3=7.2Hz), 2.66-2.75(21, i).

3.32(4, dg 3=5.3, 7.2Hz), 4.36-4.45(2H.

7.27-7.46(8. m), 7.48-7.54(2H, n), 7.55-7.73(4H. n), 7.99(2. 8.32(11, ad, 7.9Hz) 6-22 1111 Example 7 Trans-4-[(4'-trifluoromethylbiphenyl- 2 carbonyl)amino] cyclohexanecarboxylic acid c( trifluoroethylcarbamoyl)-9H-fluoren-9-yl]ethyl ester a) 4-[(4'-Trifluoromethylbiphenyl-2-carbonyl)amino]cyclo- V hexanecarboxylic acid 00 CF

CF

0 COOM

COOH

CI H 2 N'I: 3" 1 IH 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-2carbonyl)amino]cyclohexanecarboxylic acid trifluoroethylcarbamoyl)-9H-fluoren-9-yllethyl ester

O

SNH

o CF 3

CCF

0 0

HNH

CFC

The 4-(4'-trifluoromethylbiphenyl-2carbonyl)amino]cyclohexanecarboxylic acid (0.570 g) obtained in Example 7 a) and 9-(2-hydroxyethyl)-9H-fluoren-9carboxylic 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 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.

Table 57 Example I Structure NMR (8,300MHZ,CDC1,) 1.08-1.20(4H, i).

1.28-1.42(4H. m), 1.87-1.94(1. 2.80(2M, t. 3=7.1Hz), 3.52(2H. t, 3=7.1Hz). 3.65(1K, m), 3.89(1H, br), 5.18(11. d, F 3=8.3Hz), 5.25(1K, t, 3=6.4Hz). 7.29-7.79(16H.

in).

m.13. 156.3-158.0 10.60-0.71(2. i).

1.05-1.27(2H, m), 1.53-1.86(4H, 2.82(2H, t, 6.9Hz), 3.54(2H. t.

3=6.9Hz). 3.56-3.73(2H, 4.96(1. d, 3=8.3HZ), 5.27(1. t, J=7.7Hz).

7.30-7.80(16.

M).

1.33-1.73(81, m).

2.00-2.13(1. m), 2.22-2.37(1l, m), 2.45-2.60(11, 3.52(1l, t, J=7.0Hz), 3.66-4.11(4H.

5.30(11, d. J=31.3Hz), 5.72(11, t. 3=8.2Hz), 7.20-7.33(13. n).

1.09-1.20(2H. 1.24(6H.

t, J=7.2Hz), 1.36-1.53(6H.

2.27-2.38(11, i), 3.82-3.95( 1, i) 4.22(4H, q. 3=7.2Hz), 4.80(2H4, 5.21(14. br-d. 3=7.9Hz).

7.22-7.39(6. m), 7.42-7.57(4. i), 7.60-7.70(3H4 1.12-2.27(9H. 1.24(6.

t, J=7.2Hz), 2.60(2H. t, 3=7.2Hz), 3.59-3.78and3.90-4.15(11, 4.02(2H, t, J=7.2Hz).

4.22(4. q, 3=7.2Hz), 4.9Band5.3O(lH. each d.

3=8.4Hz), 7.18-7.22(13H, i) 7-4 F F

C

F

0 0 0

H

cis,trans mixture 0 Example 8 U2-Phenyl-2-(2-( 4 -[(4'-trifluoromethylbiphenyl-2carbonyl)amino]piperidin-1-yl}acetoxymethyl)malonic acid Ci diethyl ester a) 1-Benzyl-4-(4'-trifluoromethylbiphenyl-2 V) carbonylamino)piperidine 00CF 3

CF

3 SNQ

N

1 H N 0 N o 2N 00 0~ S OH N I H 4'-Trifluoromethyl-biphenyl-carboxylic acid (5.0 g) was dissolved in dimethylformamide (50 mt), and to this solution were added at room temperature 4-amnino-l-benzylpiPeridine (3.55 1-hydroxybenzotriazolehydrate 0 g) and 1-ethyl-3- (3'-dimethylaminopropyl) carbodiimide hydrochloride 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 CF

CF

3 N NJ 0

N

To a solution of the 1-benzyl-4-(4'trifluoromethylbiphenyl-2-carbonylamino)piperidine (1.47 g) Sobtained in Example 8 a) in tetrahydrofuran-methanol n mL) was added palladium hydroxide (300 mg) in a stream of argon Sunder ice-cooling. The mixture was stirred for one day at normal pressure under hydrogen atmosphere, and further stirred l for one day at normal pressure under hydrogen atmosphere after 00 Sfurther addition of palladium hydroxide (300 mg) The reaction V mixture was filtered through a Celite pad and washed with O 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-carbonylamino)piperidin-l-yl]acetic acid ethyl ester

CF

3

CF

H

To a solution of 4-(4'-trifluoromethylbiphenyl- 2-carbonylamino)piperidine (1.03 g) obtained in Example 8 b) in dimethylformamide (5 mL) were added potassium carbonate (276 mg) and bromoacetic acid ethyl ester (223 p1). The mixture was stirred overnight at ambient temperature of 90 0 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).

C d) [4-(4'-Trifluoromethylbiphenyl-2-carbonylamino)piperidin-l-yl]acetic acid 00

CF

3 S1CF, O CO 2 Et 0 CO 2

H

S N H

N

HH

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 lM aqueous lithium hydroxide (6.8 iL), 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-2carbonyl)amino]piperidin-1-yl}acetoxymethyl)malonic acid diethyl ester The trifluoromethylbiphenyl- 2 -carbonylamino)piperidin-1-yllacetic acid obtained in Example 8 d) and the 2-hydroxymethyl-2-phenylmalonic acid diethyl ester obtained in Example 1-2 a) were subjected to reactions similar to those in Example 1 g) to give the title compound (90 mg) (see Table 58).

Table 58 Example structure fNMR(8,300MH, CDC1 3 1.07-1.19(2H, 1.25(6H, t, J=7.0Hz) 1.54-1.68(2H, 2.10-2.22(2H, m), F F 2.52-2.62(2H, 3.08(2H, F 3.70-3.85(11, m), 4.24(4H, q, 8 4.85(2H, 5.07-5.16(1H, o 7.28-7.39(6H, m), 0 0 0 7.42-7.57(4H, m), 7:.61-7.71(3H, m) Example 9 2-Phenyl-2- (4'-trifluoromethylbiphenyl-2carbonyl) amino] indol-1-yl acetoxymethyl)malonic acid diethyl ester 328 in 0 Sa) (4-Nitroindol-l-yl)acetic acid ethyl ester

C)

00 Sodium hydride (60% /mineral oil:81 mg) was dissolved in Sdimethylformamide (5 mL), and the solution was cooled to 0°C.

n 5 After addition of 4-nitroindole (300 mg), the mixture was o 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 O0N OEt O0NN O0H 0 0 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) 3 -Nitroindol-1-yl)acetoxymethyl]-2-phenylmalonic acid diethyl ester SHOl t H0 2 0 0

OR

O O O2No N O o The (4-nitroindol-l-yl)acetic acid (229 mg) obtained in Example 9 4-dimethylaminopyridine (143 mg) and the

O

S2-hydroxymethyl-2-phenylmalonic acid diethyl ester (240 mg) Sobtained 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 02N Ot H 2 N N OEt 0 The 2-[2-(3-Nitroindol-l-yl)acetoxymethyl]-2phenylmalonic 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 0 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-2carbonyl) amino] indol-1-yl}acetoxymethyl)malonic acid diethyl ester CF3 o

F

3 0 n -Et H OEt 2- [2-(4-aminoindol-1 -yl)acetoxymethyl]-2- The c phenylmalonic acid diethyl ester obtained in Example 9 d) was Streated in a similar manner to Example 1 e) to give the title compound (119 mg)(see Table 59).

ci Example 9-2 n 2-(2-{2-methyl-4-[(4'-trifluoromethylbiphenyl-2- 00 1 carbonyl}amino]benzimidazol-1-yl}acetoxymethyl)-2-phenylin malonic acid diethyl ester o o Sa) 2 NMethyl 2 itroN-H-b mazole NH2

N

3-Nitrobenzene-1,2-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 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) i 2-Methyl-4-nitrobenzimidazol-1-yl) acetic acid ethyl ester IBrCH 2 COEt 02N NH N N Ot Nt N O 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- -Methyl-4- -trifluoromethylbiphefyl- 2 carbonyl.)aminO]beflZimlidaZOl11Y11acetoxYI1ethYl) -2-phenylmalonic acid diethyl ester Nt 0 Nt 0 CF 3 3 0 HNt

CF

3 HOOt 0 00 OP N N 0 o, The (2-Methyl-4-nitrobeflzimfidazol-1Yl)acetic acid ethyl ester (500 mg) obtained in Example 9-2 b) was subjected to reactions similar to those in Examples 9 1 d) 1 1 f and 1 g) to give the title compound (152 ing) (see Table 59).

Example 9-3 [2-Oxo-3- -trifluoromethylbiPhel>2'CarbOnYl) -2,3dihydrobefZOXaZOl64l]aCetic acid 2, 2-bisethylcarbarnoyl-2phenylethyl ester 332 CF 0 0 H OH l n The {3-Hydroxy-4-[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenyl}acetic acid 2,2-bisethylcarbamoyl-2- Vn phenylethyl ester (195 mg) obtained in Example 3-2 was dissolved o 5 in chloroform (5 mL), and to this solution was added triethylamine (72 mg). The solution was cooled to 0 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-2carbonyl)amino]phenyl}acetoxymethyl)-2-phenylmalonic acid diethyl ester a) 5-Chloro-2-nitrobenzoic acid chloride 0 2 N 0 2 N COOH COC1 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 Cl CI

I

0,N 0 2

,N

2 COCI COOEt Cl To a mixture of ethanol (1.23 mL), triethylamine (3.05 mL) and tetrahydrofuran (35 mL) was dropwise added a solution l n of 5-chloro-2-nitrobenzoic acid chloride (4.44 g) obtained in 00 Example 9-4 a) in tetrahydrofuran (10 mL) under ice-cooling.

V The mixture was stirred at room temperature overnight, and water o 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 sulfate and concentrated to give the title compound (4.43 g) as a pale brown solid.

c) 3-Ethoxycarbonyl-4-nitrophenylmalonic acid dibenzyl ester COOBn C COOBn COOBn 0 2 N C+ COOBn COOEt OOEt CO0Et 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 COOBn I- COOH COOBn CO0H

O

2 N 2 COOEt COOEt The 3-ethoxycarbonyl-4-nitrophenylmalonic acid dibenzyl ester (1.51 g) obtained in Example 9-4 c) was subjected o) to reactions similar to those in Example 1-3 d) to give the title compound (4.59 g).

e) 3-Ethoxycarbonyl- 4 -[(4'-trifluoromethylbiphenyl-2carbonyl)amino]phenylacetic acid CF3 CF 3 00 N 0 COOH 0

COH

S+ HN

N

SCO

O E t H COOEt 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-2carbonyl)amino]phenyl)acetoxymethyl)-2-phenylmalonic acid diethyl ester 335

O

0 COOEt NOH

OH

0 COOEt C ON 0 COOEt H COOEt iC) CF 3 00 N-- Cl COOEt N a% COOEt o H COOEt The 3-ethoxycarbonyl-4-[(4'-trifluoromethylbiphenyl- 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 2-(3-{3-Dimethylcarbamoyl- 4 -[(4'-trifluoromethylbiphenyl-2carbonyl)-amino]-phenyl}-propionyloxymethyl)-2-phenylmalonic acid diethyl ester a) 5-Methyl-2-nitrobenzoic acid chloride ON O ,N 0 OH 0 CI 5-Methyl-2-nitrobenzoic acid was treated in a similar manner to Example 1 d) to give the title compound.

b) 5, N, N-Trimethyl-2-nitrobenzamide 336 0 0,N a N 0 2 N 0 N t C 0 CI The 5-methyl-2-nitrobenzoic acid chloride obtained in V Example 9-5 a) was treated in a similar manner to Example 1 00 e) to give the title compound.

k 5 c) 5-Bromomethyl-N,N-dimethyl-2-nitrobenzamide C Br 0 N 0 2

N

O N t 0 N I

I

The 5, N, N-Trimethyl-2-nitrobenzamide (4.16 g) obtained in Example 9-5 N-bromosuccinimide (3.56 g) and 2,2'-azobisisobutyronitrile (328 mg) were suspended in carbon tetrachloride (80 mL). The suspension was stirred at 90 0 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-methoxycarbonylpropionic acid benzyl ester COOMe 0 N 0Br N COOBn 0,N

ON

0 N 0 N I

I

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).

in C( e) 3-(4-Amino-3-dimethylcarbamoylphenyl)-2-methoxycarbonyl- 1) propionic acid COOMe COOMe 0 2 N J COOBn C HN COOH o O N/ 0 N 0In SThe 3-(3-dimethylcarbamoyl-4-nitrophenyl)-2- VS 5 methoxycarbonyl-propionic acid benzyl ester (0.490 g) obtained o 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 COOMe COOMe COOH HN 0 Nt 0 N The 3-(4-amino-3-dimethylcarbamoylphenyl)-2methoxycarbonylpropionic acid (347 mg) obtained in Example e) was stirred at 150 0 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'-trifluoromethylbiphenyl-2-carbonyl)amino]phenyl}propionyloxymethyl)-2phenylmalonic acid diethyl ester 0CF COOMe 0 0 0 C 0 H O 0 N 0 t n The 3- 4 -amino- 3-dimethylcarbamoylphenyl) propionic Sacid methyl ester (0.138 g) obtained in Example 9-5 f) was V subjected to reactions similar to those in Examples 1 e) 1 f) S 5 and 1 g) to give the title compound (0.158 g)(see Table 59).

Cl 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.

339 cl Table 59 Example Structure NMR (8,30OMHzCDC1 3 1. 18(6H, t, J7.2HzL 4.15(4H, Cc, J=7.2Hz), 4.73(2H, s), 4.85(2H, 5.56(lH, d, J=3-Hz), 6.85(lH. d, 9 0WJ=3.4HZ), 6.91 (1H, d, 'fD oI J=8.3Hz), 7.16-7.78(16. 7.92(1H. d, 3=6.8Hz) 00 1.17(6H.Ht, 3=7. IHz) 2.383H.

In F F 4.13(4H. q, 3=7.1Hz), 4.70(2H, 4.87(2H, s).

6.84(11, d, J=7.9Hz), 9-2 7.12-7.63(13H, 7.80(1H, Nd, 3=7.5. 1.5Hz). 8.18(IH, d.

H0 C8- J=7.9Hz). 8.41(1. s) cx, 1.08(6H. t, J=7.2HZ) 3.27(4H F F N dg. 3=7.2 7.2Hz). 3.61(2H 0 4.88(2. 6.93(14. d, 3=1.1Hz). 7.04(14, dd. J=8.3.

9-3 0 Nr\ 1.5Hz), 7.11-7.70(15H, m), 0 0 o CH, 7.79(11, d. 3=8.3Hz) 1.21(6H, t, J=7.1Hz). 1.35(3H.

F t, 3=7.1Hz), 3.55(2H, s), 4.15-4.30(6H, m) .4.83(2H, s).

0 7.24-7.38(6H. m).

9-4 07.41-7.47(1l, m).

9-4 o c, 7.48-7.62(6. 7.76(1 1. dd.

H CHI 3=1.5, 7.5Hz). 7.81(11, d.

0 3=1.9Hz), 8.68(14, d, J=8.7Hz), 11.23(14, br-s) 1. 24(6H, t. 3=7. OHz) 2. 53(2H, t. 3=7.3Hz), 2.76-3.00(6H, F F 01% br), 2.81(2H. t. 3=7.3Hz).

FK4. 24(4H, q, J7. OHz) ,4.81( 2

H,

N 0 6.96(114, d, J=2.3Hz).

0 7.17(I ad. J=1.2, 8.4Hz) 0 7.29-7.37(5H, m), I 7.37-7.42(lH, m), I 7.44-7.57(2H, m), CN 7. 60-7.64(4H, M) 68(IH, dd, 3=1.5. 7.4Hz). 8.28(1, d, 3=8.4Hz), 9.05(14, br-a) Table 60 Example Structure NMR (b,3oo1mz,CDC1 3 1.12(6H, t,3J7.2Hz), 3.30(4H4, F dq. 3=5.7, 7.2Hz), 4.39(2H1, d, 3=6.0Hz), 5.08(2H1, 0 5.59(114, br-t, 3=6.0Hz), 9- 6.97-7.03(2H, in), 9-6 7.28-7.42(811, in), 0 7.43-7.55(4H. mn), 0 0 7.56-7.61(2H, in), 7.6 7.1 lH 7.76-7.83(2H1, in) 1.08(3H1, t, 3=7.2Hz), 2.64-2.82(2H, in), F F 2.86-2.97(2H, in), 3.13-3.36(2H1, mn), 5.57-5.98(111, br), 6.03(111, A9-7s) 7.00(111, 7.04-7 .15(41, No 0 n) 7-30-7. 40(5H1, in), 7 .43(111, A N Gd, J=1.1, 7.48-7.63(4H, in), 7. 63-7 .71( 2H, mn), 7. 78( 11, dd, 3=1.5, 7.SHz) 1. 04 (6H,t,3J=7. 2Hz) 3 .23 (4H4, FF Ndq, 3=5.7, 7.2Hz), 3.55(2H4, ,4N 4.85(2H1, 5.23(2H1. s), a A 7.08(2H1, br-t, 3=5.7Hz), 0 7.14-7.22(2H, in), 9-8 N T O 0 NH 0 7.23-7.47.(10H1, m), 0 0 N 7.48-7,64(6H, mn), 7.76(1H, dd, N 3J=2.2Hz), 8.69(114, d, A 3J=8.7Hz), 11.17(111, br-s) F F N1.05(6H, t,3=7.21z), 3.25(4H1, F dq, 3J=5.6, 7.2Hz), 3.58(2H1, 0 4.86(2H1, s), A- 0 A 7.11-7.63(151, mn), 7.72(111, NI NN 0 NH d d, J=1.5, 7.5Hz), 7.83(1H, d, 14 r-3=1.9Hz), 8.66(1H, d.

HO 0 3F =8.6Hz), 11.10(111. br-s) 1.07(6H, t,3J=7.2Hz), 1.36(3H4, F F t, 3=7.2Hz), 3.26(4H1, dq, F 3=5.4, 7.2Hz), 3.58(2H1, s), N 0 4.26(2H1, g, 3=7.2112), 4.86(2H4, 9-10 A0 7.1.0(2H1, br-t, J=5.4Hz), N 7.16-7.37(6H, in), N N N H 0 Sc 7.40-7.64(71, in), 7.77(111, ad, A H 3=I9 7rH),7801_d 0 a C. J19 .0ld 3e1.9Hz), 8.69(114. d, 3=8.7Hz), 11.22(111, br-s) rn-t-1 Cl 0.2.

TI -uie 6r Example Structure NMR (8.3OMHz,CDC13) 1.19(6H, t, J7.

2 H2), 4.17(4H, F F q, 3e7.2Hz). 4.79(2H, s), 4.90(2H, 6.94(11, d, 3c8.OHz), 7.15-7.63(13H, i), 9-11 7.82(1, d, 3=7.5Hz), 8.25(1*, H N N 0 0 CH d, 3=8.0Hz), 8.47(11, br.s) X15(6H, t, J=7.2Hz), F F 2 6 4-2.73(2 m) 3.32(4H, dq, F 3=5.3, 7.2Hz), 4.31-4.44(2H, 4.41(2H. d, 3=6.0Hz), 0 A5.62(11, br-t. 3=6.0Hz), 9-12 7.10-7.16(1H, m), A 7.24-7.39(7H, m).

7.42-7.58(6H, m), 7.62-7.72(3H, i), m.p 139.4-141.0 7.74-7.78(11, m), 7.55-7.92(11, m).

1.07(6H, t, J=7.IHz) 3.26(4H, NF dq, J=5.7, 7.1Hz), 3.57(2K, F A 3.81(3H, 4.86(2H, s), 0 7.10(6H*, br-t, J=5.7Hz), 9-13 A a7.16-7.23(2B, m), N i4-\ 7.25-7:37(4. m), N N "H c%7.41-7.63(7*, 7.77(1*. dd, HP 3=1.5. 7.5Hz), 7.80(1*, d, A=2.2Hz), 8.68(1, d, 3=8.3Hz), 11.15(11, br-a) F 1.19(6H, to 3=7.0Hz), 3.5 2 (2H, F 4.19(4H, q, 3=7.0Hz), A 4.82(2H, 5.23(2H, a), A a 7.24-7.29(5H, m), o A4 7.32-7.46(7H, m), 9-14. N N N9 2 0. 0 C 7.49-7.62(6H, m), N 7.74-7.79(11, 7.82(11, a, A=2.2Hz), 8.67(11, d, 3=8.8Hz), 11.17(1*, br-s) F F 1.21(6H, t, 3=7.1Hz), 3.56(2H, 4.21(4H, =7.1Hz), a 4.85(2H. 7.23-7.32(5*, m), 9-15 0 0 7.36-7.63(8H, m) 7.77O1H, dd, N 0 7.5Hz), 7.86(1, a, H *7 J=1.9Hz), 8.70(1H, br-d, 0 H 0 O=8.3Hz), 10.89(1*, br-s) Table 62 Example Structure NNR (6,300NHz.CDC- 3 F F 1.22(6H, t, 3=7.1Hz), 3.57(2H, F 0 4.23(4H, g. 3=7.1Hz) 4.85(2H, 6.92(1H, s), 9-16 0 0 0 7.03(11. d, J=8.3Hz), N 0 7.30-7.69(13, 7.77(11. d, 3=8.3Hz) 0 F F.23(6H.t, 3=7.IHz), 3.67(2H, F 4.23(4H, q, J=7.1Hz), 4. 85(2H, 7.23-7.34(6H, in).

0 7.42-7.49(3H. M), 9-17 N 7.52-7.67(5H, 7.95(11, d, N a 8.05(11, ad. 3=1.5, 0

CH,

1.21(6H. t.3=72Hz), 1.31(6H, F F d, =6.4Hz). 3.55(2R, s), C 0 4.21(4H, q, J=7.2H), 4.83(21.

sa). 5.09(11,.sept. 3=6.4Hz), 9-18 0 a H, 7.24-7.38(6H, m), Ir 'ci, 7.41-7.47(1l, m), a 7.48-7.62(6H, i), HC C01 7.73-7.81(2H, 8.68(1, d, 3=8.6Hz), 11.33(11. br-s) 1.21(6H, t, 3=7.1HZ). 3.54(2H, F F 3.80(3H, 4.21(4H, q, 3=7.1Hz), 4.83(2H, s), 9 C I 1 7.24-7.38(6H, 7.44(1H,dd, 9-19 0 l, J=1.6, 7.Hz), 7.50-7-2(6H, 7.77(11, dd, 3=1.5, 0 7.1Hz), 7.81(1H, d, 3=2.3Hz), CH, 8.67(11, d, 3=8.7Hz), 11.15(11, br-sI 1.21(6H, t. 3=7.1Hz), 1.85-2.03(2H,rm).2.05-2.27(2H.

F F 2.50-2.67(11. 2.81(3H, bra). 2.88(3H, bra)..

0 3.02-3.16(11, 3.51(2H. a).

3.71-3.86(11, mn), 4.20(4, q, 9-20 0 CKY s J=7.1Hz), 4.82(2H, 6.99(1.

H a K. d, J=9.0Hz), 7.05(11, d. 3=1.8 0 r-Hz), 7.18(11, dd, J=1.9Hz 3=8.3Hz). 7.22-7.37(5H, m), 7.56(1, dd. 3=1.81. 3=9.0Hz), 8.01(1H, brs). 8.08(1. d.

3=8.3Hz), 9.29(1. bra).

343 Table 63 Example Structure NMR (6,300MHz,CDCl 3 1.18(6H, t. 3=7.1HZ), 2.03(3H, F 3.53(2H, 4.14(4HI,.

0 J=7.1Hz), 4.86(2H. s), 0 6.97-7.05(2H!. in), 9-21 N0 CH3 7.24-7.81(15H, 8.35(1H, N K brs).

H01 0 OyNH

CH.

1.20(6H, t,3 J7.2H), 3.52(2H, P FN 3.72(30, 4.18(4H, q.

0 -3=7.2Hz), 4.83(2H, s), 6.83(1H, brc), 4.95(1H, dd, 9-22 0 1\ CH. Jd1. 8Hz, 3=8.3Hz). 7.14(1H, d, 0 V J=8.3Hz)y 7.18-7.80(15. m).

y- mp 146.4-148.6 OMo F F 1.20(6H, t, J=7. lHz) 2.36(3H, F 3.57(2H, 4.20(4H, q, N g0 3=7.1Hz), 4.85(2H, s).

0 0 6.85(1l, 7.-18-7.59(14H, 9-23 N 0 c 8.67 (IH, d, 3=8.6Hz) A 12.71(1H, brs) S \N

CHSN

1.19(6H, t, J=7.2Hz), 3.53(2H.

F 4.17(4H, q, J=7.2Hz), N4.82(2H, 6.89-6.96(3H, m), 0-11 7.17-7.55(17H, 7.67 (1H, 9-24 0 0-43 dd, a=1.5, 7.5Hz), 8.45(1H, N N N0=8.7Hz) 1.21(6H, t, J=7.1Hz) ,3.59(2H, 4.21(4H, q, 3=7.1Hz), F F N4.87(2H. 7.27-7.7(15H, 8.67(11, d, 3=8.3Hz), 909.61(1H, brs), 11.1(14, brs) 9-25 A i 00 0 H 0 CCH. 0 L c 344 Table 64 Example Structure NMR (5,300Mz. CDC1,) 1. 20 (6H, t, J=7. 0Hz), 1. 94(6H, F F 3.14(2H, 3.48(2H, s).

F 4.19(4H, q, 3=7. OHz) 4.81(2H, 0 6.83(1H. d, 3=2.0Hz).

9-26 A 0~ 7.08(1K, dd, 3=2.0, 'S0 0L N 0 0 o% 7.27-7.59(12H, 7.68(1K.

H Ndd, =1.

2 7.6Hz), 8.22(1, d, 3=8.5Hz), 10.7(1W, brs) 1.21(6H, t, J=7.1HZ). 3.20(3H FF 3.36(3H, 3.52(2H, a), 4.21(4H, q, 3=7.1Hz), 4.82(2H, a 7.23-7.61(14. m), A2o 0 7.71(1H, d, 3=7.3Hz). 8.31(1H, 9-27 0 d, 3=8.4Hz), 9.49(1K, bra) F F 1.06(6H.d, 3=6.9HZ), 1.20(6H, F t 3=7.2Hz), 3.42-3.51(1H. m), A 3.56(2H, 4.20(4H, q, 0 3=7.2Hz), 4.85(2H, s), 9-28 o- 7.28-7.77(15H, m) 8.72(1H, d.

I c1% 3=8.7Hz), 11.81(1, brs) ca cs 0.49(3H, d, J=6.6HZ), 0.90(3H, F F d, 3=6.6Hz), 1.14-1.25(6H, m) A 1.40-1.58(1H, 2.41(1K, d, 0 3=3.6Hz), 3.51(2H, A-2A 0 0 3\=3.6Hz), 3.81-3.88(114, m), 29 0 90 4.02-4.18(4H, 4.83(2H1, s), 04 6.79(H, 7.05-7.69(14

H,

HOm), 8.19(H, d. Jb8.r)z) CC11 9.01(1H, brs) 345 Table compound structure NMR(6, 300MHz, CDCI1) F F 2.86(3H, brs), 2.93(3H, brs), 3.56(2H, s).

e j OH 7.09(1H, d, 2 e) 0 7.23-7.71(9H, m),

N

I H 8.29(1H, d, J=8.7Hz), 0 9.06(1H, brs).

F 1.75-1.99(4H, m), F 3 3.32-3.52(4H, m),3.53(2H, s).

H 7.20-7.69(10H,

OH

2-17 e) 0 0' 8.22(1H, d, J=4.4Hz), N/ 0 9.74(11H, brs).

I H Or.

Formulation Hereinafter, the present invention will be illustrated specifically by references of formulations.

Formulation 1 A film with a controlled thickness was prepared by use of a gelatin shell composition in accordance with the conventional method. Two sheets of the film were inserted into a rotating left-right symmetric metallic die rolls and molded into outer shells of soft capsules, while a filling solution was injected into the outer shells of the soft capsules, and simultaneously the outer shells of the softcapsules were 346 0 o melted and sealed by the rotation of the die rolls, then the ci capsules were cut from the film. The capsules were dried in a rotary dryer, and allowed to dry for 4 days to give soft Ci capsules. Hereinafter, specific examples of formulations were given.

I Formulation 1-1 00 film composition C) gelatin 100 parts kn Ssugar alcohol solution derived from corn starch 30 parts purified water 100 parts filling solution (per capsule) propylene glycol fatty acid ester 295 mg ethanol 105 mg Formulation 1-2 film composition gelatin 100 parts sugar alcohol solution derived from corn starch parts purified water 100 parts filling solution (per capsule) compound of Example 2-5 5 mg propylene glycol fatty acid ester 291 mg ethanol 104 mg Formulation 1-3 film composition gelatin 100 parts sugar alcohol solution derived from corn starch parts 0 purified water 100 parts 0 filling solution (per capsule) compound of Example 2-5 5 mg Ci propylene glycol fatty acid ester 277 mg ethanol 148 mg VI Formulation 2 00 The compound of Example 2-22, an excipient and a binder C were mixed in a usual method to prepare granulated powder. The o 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 0 hydroxypropyl methylcellulose 2910 6 mg Scalcium silicate 20 mg crospovidone 10 mg CI magnesium stearate 0.6 mg SPharmacological test 00 Test Example 1 NInhibition of interliposomal triglyceride (TG) transfer o 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% NaN 3 (pH 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 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 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 minutes, then centrifuged at 10,000 x g 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 0 mol% triolein, 5 mol% cardiolipin) labeled with "C-triolein Sand non-labeled SUV liposome (acceptor, 0.25 mol% triolein) were prepared. A fixed amount of donor and acceptor, and MTP C were mixed with a sample dissolved in DMSO or with DMSO. The mixture was incubated in a 15 mM Tris hydrochloride buffer (pH S7.4) containing 40 mM sodium chloride, 1 mM EDTA 0\ 0 0 (ethylenediaminetetraacetic acid), 0.02% NaN 3 and 0.5% bovine Sserum albumin at 37 0 C for one hour. After completion of the o 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 rite 100 x (1 minus ((radioactivity of sample group minus radioactivity of blank group)/ (radioactivity of DMSO group minus radioactivity of blank group))).

Inhibition rate (ICso) was determined on the basis of the above equation. The results were shown in Table 66 to c Test Example 2 Inhibition of apolipoprotein B secretion from HepG2 cells HepG2 cells were suspended in Dulbecco's Modified Eagle's Ci Medium (DMEM)(containing 10% fetal bovine serum, 100 units/mL penicillin and 100 C[g/mL streptomycin), and placed on a 96-well 0 V plate (4 x 104 cells/well), then incubated for 24 hours. After 0 0 removal of the medium, DMEM was replaced by a medium containing a sample dissolved in DMSO or a medium containing DMSO o (concentration of DMSO: 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 g/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 L/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 PL/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 [L/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 jL/well) was placed in the well, and allowed to C stand at room temperature for one hour. The reaction was stopped by addition of 2% oxalic acid (100 pL/well), and absorbency at 405 nm was measured. Concentration of apo B in

C

N the sample was calculated on the basis of a standard curve of the standard. Inhibition rate was calculated from the V) assayed values in accordance with the following equation.

00 Inhibition rate 100 x (1 minus (concentration of I) apo B in sample group/concentration of apo B in DMSO group).

0 Based on the above equation, 50% inhibition concentration

(IC

50 was determined.

The results were shown in Tables 66 to 352 Table 66 Test Example2 Test Example 1 Test Example 2 Test Example I Inhibition of Inhibition of Example P i Example Mnion Example KTP inhibition apo B secretion

IC

3 0 (nM) Ipo secriom) IcSn (IC 50 (niM) I 0.6 5.8 1-2 42 850 1-3 4.7 5.75 1-4 3.4 190 0.66 0.65 1-6 1.2 1-7 7.55 330 1-8 37.5 720 1-9 5.95 3.2 1-11 32 22 1-12 7.6 63 1-13 5.8 170 1-14 82 55 1-22 66.5 179.5 1-23 54 63 1-25 5 8.4 1-26 630 620 1-27 7 26 1-28 35 640 1-31 84.5 61 1-32 8.6 720 1-34 23 100 1-35 1.0 6.9 1-36 2.0 250 1-37 3.5 47 1-38 6.0 320 1-39 0.66 160 1-40 6.9 2.1 1-42 4.4 35 1-45 0.39 0.46 1-47 4.5 750 1-48 3.2 9.7 1-49 20 5.3 1-51 0.96 530 1-52 10 690 1-53 0.43 860 1-62 5.0 46 1-63 16 1-66 16 9.3 1-67 27 28 1-69 9.1 90 1-70 1.6 270 1-71 1.8 120 1-72 0.44 2.7 1-73 39 1-74 680 Table 67 Test~~ Exml etEape2Ts xml Test Example2 TetExample 1 ibto Inhibition of Ts Example Tes Exampeito Inhibition of Exampl KTP niito epo B secretion xaplOMP niito apo B secretion 1C 5 0 (901n) 1 I1 5 (M

C

50 (nx) 1-75 1-77 1-79 1-al 1-83 1-85 2 2-3 2-8 2-12 2-14 2-16 2-19 2-21 2-23 2-25 2-29 2-31 2-33 2-35 2-39 2-41 o.62 2.1 1.4 1.8 2.7 0.74 97 360 0.59 0.49 0.23 3.2 1.5 2.0 0.55 o0.99 7.0 1.2 2.7 26 1-76 1-78 1-80 1-82 1-84 2-2 2-4 2-7 2-10 2-13 2-15 2-18 2-20 2-22 1.4 0.94 1. 1 1.4 120 11 8.2 0.53 4.4 1.3 o.29 0.56 1.4 0.74 0.53 0.69 0.64 0.44 0.61 2-24 28 6.3 2-26 8.2 91 2-30 27 43 2-32 1.7 13 2-34 38 2-36 -7.4 0.76 1.2 2-40 2-42 0.99 1.8 I I I Table 68 Test Example 2 Test Example 2 Test Example 1 ibitioTet Example 1 nhibition of Example MTP inhibition apo Bsecretion Example MTP inhibition apo B secretion Example IP inhibition apo B secretion

IC

5 (nM) IC 5 (nM) ICso(nM) IC 5 (nM) I C IC M) 2-43 9.0 2-44 33 2-45 39 2-46 2.9 2-47 1.2 2-48 0.36 2-49 49 2-50 21 2-51 47 2-53 4.6 2-54 -8.5 2-55 4.2 2-56 0.93 2-57 0.56 2-58' 1.9 2-59 0.99 2-60 1.3 2-61 0.38 2-62 0.37 2-66 57 2-67 -43 2-68 2.25 2-69 0.91 2-70 2.34 2-71 0.54 2-72 0.95 2-73 -2.93 2-74 0.84 2-75 -12.54 2-76 0.85 2-77 2.74 2-78 -0.14 2-79 1.3 2-80 0.79 2-81 0.96 2-82 4.41 2-83 8.87 2-84 -2.01 2-85 -0.49 2-86 -0.42 2-88 1.92 2-90 1.74 2-91 0.54 2-92- 1.47 2-93 45.8 2-95 18 355 Table 69 ~Test Example 2 Test Example 2 Test Example 1 Inhibition of Test Example Inhibition of Example MTP inhibitiono Example MTP inhibition apo B secretion ple MTP apo B secretion ICs 0 (nM) IC (nM) IC(nM) IC 50 (nM) 2-96 81 2-97 -22 2-98 0.97 2-99 19 2-102 14.63 2-103 -42.6 2-104 358 2-105 0.2 2-106 -0.44 2-107 2-108 -0.82 2-109 0.93 2-110 -0.65 2-114 3.1 2-115 44 2-117 38 2-118 49 3 1.9 3-2- 4.2 3-3 0.40 1.0 3-4 2.1 13 2.2 3-6 5.0 0.63 3-7 0.35 3-8 3.7 0.38 3-9 1.6 3-10 2.7 0.31 3-11 -0.36 3-12 0.72 3-13 -1.9 3-14 13 64 3-15 49.9 4 0.33 4-2- 16 4-3 7.9 4-5- 5.2 4-6 -7.5 4-7 4-8 10 3.1 19 5-2 66.5 875 5-3 6.2 86.5 5-4 2.4 57 356 Table TetEapeITest Example 2 Test Example 1 Inhitio ofmpe TetExample 1T nibto Inhibition of Exaple wrP inhibitionInitonf 1C 50 (am) apa Bsecretion

IC

5 O (nm) ap Bscretion

C

5 0 (nM) -CO

M

4.5 5.0 5-6, 3.9 260 5-8 14 340 5-9 4.0 28 5-10 6.2 300 5-11 1.3 5.1 5-12 1.3 5-13 2.4 5-14 -0.34 5-15 -6.4 5-16 3.0 5-17 5.2 6 3.47 58.3 6-3 5.2 510 6-8 50 630 6-10 22 870 6-14 6,.3 87 6-15 2.0 57 6-16 2.9 170 6-17 2.3 420 6-19 3.2 35 6-21 9.8 920 7 4.97 60.0 7-2 2.46 26 16.2 237 8 33 595 9 11 260 9-2 4.2 450 9-3 -59 9-4 9.9 -3.1 9-6 59 9-8 6.9 9-10 2.3' 9-11 20 210 9-13 0.53 9-14 41 9-17 23 9-21 -20 9-22 -0.96 9-23 -8.77 9-24 -7.86 9-27- 0.82 c Test Example 3 UOlive oil-loading test SSyrian hamsters (9-11 weeks of age) under non-fasted (C conditions were used in the test. Blood was collected previously from orbital venous plexus, and a sample was I suspended in 0.5% methyl cellulose (vehicle) and the suspension 0 0 was forced to be administered orally to the hamsters at a dose c of 0.3, 1i, 3 or 10 mg/2 mL/kg. Only vehicle in the sane volume o 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 The data was expressed in terms of ATG(mg/dL)=the value at 4 th hr minus the value before administration. Inhibition rate was calculated from the data obtained on the basis of the following equation.

Inhibition rate x (1 minus ATG of sample group/ATG of control group). The results were shown in Table 71.

358 Table 71 Test Example 3 Test Example 3 Inhibition of fat inhibition of fat Example absorption after Example absorption af ter olive oil-loading in olive oil-loading in Hamster (flmg/kg.p.O) Hamster (()mg/kg.p.o) Inhibition rate Inhibition rate (t) 1 57(100) 1-3 65(100) 59(3) 1-6 .54(10) 1-35 59(100) 1-45 71(100) 1-66 52(100) 1-72 54(100) 2 95(10) 2-2 96(10) 2-3 68(3) 2-4 178(3) 70(3) 2-7 58(3) -2-8 89(3) 2-13 70(3) 2-14 80(3) 2-15 81(3) 2-la 58(3) 2-22 61(3) 2-25 55(3) 2-39 68(3) 2-48 87(3) 3-3 78(10) 3-5 80(10) 3-6 52(3) 3-7 74(3) 3-8 60(3) 3-10 85(3) 3-11 75(3) 5-9 78(100) 5-11 64(100) 9-10 54(3) 9-13 70(3) c Test Example 4 Liver TG release inhibition test Q 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 0\ a sample was forced to be administered orally to the hamsters 00 at a dose of 30, 100 or 300 mg/2 mL/kg, and the same amount of Svehicle was administered to the control group. Triton WR 1339 o (2 mL/kg) was intravenously administered to the hamsters 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 The data was expressed in terms of TG release velocity (mg/dL/min)=(value at 2 nd 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 (I minus TG release velocity of sample/TG release velocity of control group). The results were shown in Table 72.

CI Table 72 Test Example 4 Test Example 4 Inhibition of liver TG Inhibition of liver TG release in Hamster release in Hamster No. No.

o (()mg/kg.p.o) inhibition rate( Inhibition rate(%) 00- 19(300) 1-6 0(i00) 1-35 9(300) 2-5 0(100) 2-22 0(30) 2-39 6(100) 3-3 18(100) Test Example Combination use test Japanese white rabbits (male, 19 weeks of age, JW, purchased from Kitayama Labes Co., Ltd.) were fed previously in such a way that they were fed a high cholesterol diet (0.3 cholesterol 3 peanut oil-added RC-4, Product of Oriental Yeast Co. Ltd. of 70 g/day under limited feeding for one day.

The rabbits thus fed were used as a cholesterol-loaded rabbit model, and the grouping of such model was carried out in such a way that there might be no variation in the amount of plasma cholesterol among each group (five rabbits/group). After collection of blood from auricular artery, compounds of Examples 2 to 5, simvastatin, and compounds of Examples 2 to plus simvastatin were added to a high cholesterol diet in the dose as shown in Table below, and the rabbits were fed such diet.

The rabbits were fed 70 g of each diet every morning. Blood (N was collected from auricular artery 6 hours after the feeding o on the 4 th 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 4 t h day was shown.

STable 73 00 Increased amount of V' total cholesterol o .(mg/dl) Control 80.0 Simvastatin (1 mg/kg) 48.6 Example 2-5 (10 mg/kg) 8.6 Example 2-5 (10 mg/kg) 2.1 Simvastatin (1 mg/kg) 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 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.

Table 74 Blood of portal Peripheral blood Dose Compound Component vein (pM) (pM) (mg/kg) lh 2h 4h lh 2h 4h Unaltered <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 1-2 30 form Metabolite 1.6 2.2 6.7 0.9 1.3 2.9 Unaltdred <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 1-12 30 form Metabolite 11.8 18.2 24.4 7.3 12.1 15.4 Unaltered <0.2 <0.2 <0.2 <0.2 <0.2 <0.2 1-13 30 form Metabolite 11.8 20.6 27.3 10.9 16.9 18.3 Unaltered 0.01 0.03 0.01 <0.02 <0.02 <0.02 2- 3 f r

I.-

30 form Metabolite 0.33 0.73 0.38 0.01 0.01 0.02 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 P-nicotinamide adenine dinucleotide phosphate: 1.3 mM, D-glucose-6phosphate: 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.

(c The solutions were incubated at 37 0 C for 0, 10 and 60 minutes, and an organic solvent was added thereto. The solutions were Scentrifuged, and the concentration of the sample (unchanged C 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 00 the following equation.

IRemaining rate(%)=amount of sample 10 or 60 minutes after 0 Sincubation/amount of sample at zero time after incubation x 100 Table human hamster Remaining Remaining Remaining Remaining rate rate rate rate after 10 after 60 after 10 after min. min. min. min.

Small intestine 97.6 91.5 29.0 14.1 S9 Liver S9 7.9 4.3 2.4 0 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 below.

Table 76 T? inhibition Inhibition of Compound main metabolite apo B secretion

IC,,

0 (fM) IC 50 (nfl) F F

F

0OH >1000 >10000 0

N

0 HO >1000 >10000 CH 3 F F

F

0OH >1000 >10000 1-30 0 HO0 >1000 >10000 H N 0 NH IN O-H 3

OH

3 0 0 ci

C-)

C)

en ci 0 00 ci 0 0 ci Table 7 7 Inhibition of

MTP

apo B Compound Main metabolite inhibition secretion F F

OH

O0 >10000 >10000

N

H cH 0 N -0 HO0,\C >1000 >10000 0

CH

3 F F

F

NOH

0 O >10000 0NN 2-17 0 HO4 >1000 >10000 NNCh

OH

366 Table 78 HTP Inhibition of Compound Main metabolite inhibition apo B secretion ICsa(nM) ICso(nM) F F

F

H

3-4

HC

/o HO O >1000 >10000 O CH, 0 3

CH,

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 0 0 (N are present in portal vein in a very small amount, and since 0 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 00 moiety of these metabolites is cleaved by hydrolysis and thus ci Vthey have little or no MTP inhibitory activity. Further, Test 0 O Example 5 reveals that combination use of the compounds of the ci 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 368 o compounds of the present invention do not affect liver MTP, O accumulation of triglyceride does not occur in the liver.

S Consequently, inhibition of fatty liver generation as an c- adverse effect might be expected. Therefore, the compounds ofthe present invention can be said novel MTP inhibitors having

O

I' no side effects such as a fatty liver, etc. or, in-other words, 00 they are novel agents for the treatment or prophylaxis of Cl hyperlipidemia, arteriosclerosis, coronary artery diseases, o 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.

A reference herein to a prior art document is not an admission that the. document forms part of the' common general knowledge in the art in Australia.

In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

Claims

4- K KNA- NA-'N AL~- N f K 4 N~ N A- N N K N N N~ 4) N H S 4C- N =4 -4 N 0 ZDE- wherein K is an integer of 0 to 2, or ring B may be taken together with R 3 R10 and the nitrogen bound to R10 to form Alkll is alkanediyl or alkenediyl; Alk12 is alkanediyl or alkenediyl; I is an integer of 0 to 3; m is an integer of 0 to 3; D is C 1 -C 6 alkyl C 2 -C 6 alkenyl, C 2 -C 7 alkoxycarbonyl, -N(R )-CO(R 4 (wherein R 42 is hydrogen or CI-C 6 alkyl and R 4 is C 6 -C 14 aryl or C7-C 16 aralkyl). or the group represented by the Sfollowing formula R 6 R7 OC 00oo In O 5 (wherein R s R 6 and R 7 are each independently hydrogen, Cz-Cs alkyl. Ci-Cs alkoxy, C 2 -C7 alkoxycarbonyl. carboxyl. halogen, cyano, nitro, halo C 1 -C 6 alkyl. Ci-C 6 acyl, hydroxy, amino, optionally substituted C 6 -C 14 aryl, or -(CH 2 )r-CON(R 1 (R 17 (wherein R 16 and R 17 are each independently hydrogen, C 1 -Cs alkyl or halo C 1 -C 6 alkyl and r is an integer of 0 to 3); ring C is C 6 -C 14 aryl, C7-C15 arylcarbonylamino, CB-C 1 7 aralkylcarbonylamino, heterocycle residue, C 3 cycloalkyl or C7-C 16 aralkyl, or ring C may be taken together with R 7 and R B to form and R 8 and R 9 are each independently hydrogen, Ci-C 6 alkyl, optionally substituted C 6 -C 14 aryl, hydroxy CI-C 6 alkyl, -CON(R 8 (R 19 )(wherein R 18 and R 19 are each independently hydrogen, Ci-C 6 alkyl, C 3 -C 7 cycloalkyl, halo Ci-C 6 alkyl, C 2 C 2 alkoxyalkyl or optionally substituted C 6 -C 14 aryl), -COO(R 20 or 373 0 CN -(CH 2 )s-OCO(R 20 )(wherein R 2 0 is hydrogen, CI-C 6 alkyl or C 3 -C 7 cycloalkyl; s is an integer of 0 to -N(R 21 (R 22 (wherein.R Sand R 22 are each independently hydrogen, Ci-C 6 alkyl, C 1 -C 6 acyl, C CI-C 6 alkylsulfonyl, or R 21 and R 22 may be taken together with S 5 the nitrogen to which they are attached to form 0 00 N 0 or R 8 and R 9 may be taken together to form C 3 -C 7 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 claim 1, wherein D is CI-C 6 alkyl, C 2 -C 6 alkenyl, C 2 alkoxycarbonyl or -N(R 42 -CO(R 4 3 in which R 42 and R 43 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 claim 1, wherein D is the group represented by the formula R6 R7 C in which R 5 R 6 and R 7 each has the same meaning as defined above. O S4. The ester compound or a prodrug thereof, or a Spharmaceutically acceptable salt of either according to claim 3, wherein the ring C is N or 0' a O r ,in which q is an integer of 0 to 3. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 2 or claim 4, wherein ring B is or Ars
6. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to according to claim S, wherein ring A is or S
7. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 6, wherein X is -CON(R 0 )-(CH 2 in which R 10 and n each has the C< same meaning as defined above.
8. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 6, wherein X is -COO-(CH 2 in which n has the same meaning as defined above; 00
9. The ester compound or a prodrug thereof, or a o pharmaceutically acceptable salt of either according to claim 7 or claim 8, wherein n is 0. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is represented by the formula s R6 C R7 RR 3 X R9 wherein R 2 and R 2 are each independently hydrogen, Ci-C 6 alkyl, C 3 -C 7 cycloalkyl, Ci-C 6 alkoxy, halogen, halo Ci-C 6 alkyl, Ci-C 6 acyl, C 2 -C6 alkenyl or cyano; Xi is or -NR' 0 wherein R 10 is hydrogen, Ci-C 6 alkyl or C 3 -C 7 cycloalkyl; and R 1 R 3 R R 5 R 6 R, R 8 R 9 ring C, 1 and m each has the same meaning as defined above, A or a prodrug thereof, or a pharmaceutically acceptable salt of C) either.
11.' The ester compound or a prodrug thereof,. or a pharmaceutically acceptable salt of either .according to claim n 10, wherein the ring C is 00 or 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 claim 11, .wherein KX is -NR 1 0 in which R' 0 has the same meaning as defined above.
13. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either .according to claim .11, wherein Xi is
14. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims 10 to 13, wherein the group -(CH 2 is located at the h-position of-the benzene ring in the formula 377 O :15. The ester compound or a prodrug thereof, or a o pharmaceutically. acceptable salt of either .according to any. 0 one of claims 10 to 13, wherein the group -(CH 2 is located Sat the i-position.of the -benzene ring in the formula Cr)
16. The ester compound or a prodrug thereof, or a Spharmaceutically acceptable salt of either according to any i one of claims 10 to 15, -wherein R and R 9 are each 00 S independently -CON(R') in which R" and R 19 each has the 0 same meaning as defined above. C 17. The'ester compound or a prodrug thereof, or a pharmaceutically acceptable'salt of either according to any one of claims-10 to 15, wherein R and R 9 are each independently -COO(R 2 in which R 20 has the same meanig as defined above.
18. The ester compound or'a prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims 12 to 17, wherein the ring C is C 6 -C 14 aryl.
19. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim wherein C 6 -C14 aryl.is.phenyl. The-ester compound or a prodrug thereof, or-a pharmaceutically acceptable salt of either according' to any one of claims 12 to 17, wherein the ring C is C 3 -C 7 cycloalkyl.
21. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims 378 CI 12 to 17, wherein the ring C is o N N
22. The ester compound or a procirug thereof, or a 00 pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of o(4- W trif luoromethyl-b5PhenYl2-carbonYl) -amino] phenyll-acetic acid 2, 2 -bis -ethylcarbamflY12T7Phefl>ethyl ester, 2-phenyl-2-(2- -trifluoromethY1-biPh~nfl 2 carbonyloxy) -phenyl I-acetoxymuethyll -malonic acid diethyl ester, 2-C 2-{3-methyl-4- -trifluoromethy1-biPhenYl- 2 carbonyl) -amino) -phenyl}-8cetoxymfethYl) -2-phenyl-YfalOnic acid diethyl ester, 2- [methyl- -trifluorornethY1-biPhenYJ- 2 carbonyl) -amino] -phenyl -acetoxymethyl) -2-phenyl-laL~lic acid diethyl ester, {3-ethyl-4- [(41 -trifluoromethY1-biphel1 2 -carbonYl) amnino] -phenyll-aCetic acid 2 ,2-bis-ethylcarbamfoYl- 2 phenyl-ethyl ester, rfuroehlbihnl2-abnl-amino] phenyl)-acetic acid 9-C 2,2, 2-trifluoro-ethYlcarbamoyl) -9H- fluoren-9 -ytmethyl ester, -trifluoromethyl-biPhelYl-2-CarbonYX) amino] -phenylll-propiOflic acid 9- (2.2 ,2-trifluoro- ethylcarbaloyl) -9H-fluoref-9-ylmethYl ester, -trif luoronethYJ-bihnl-2hen ony) arricJ phenyll-acetic acid 2-pheny--(2. 2,2-triflUOrO- en ethylCa-rbafOYl)-ethYl ester, o 5 carbonyl) -amino]I -phenyl) -acetorymethyl) -maloflic acid diethyl ester, 00 trif luoromthYl -biphenylI-2-carbonyl) ami-no]I V')phenyid-acetic acid 1- 2-trifluorO-ethY1CdarbamoYl) o cyciopentyJlmethyl ester. 2-phenyl-2- -trifluorOmfethYlI-biPhenYl- 2 carbonyl) -amino] -pheny1}-aCetOXYfllthYl) -maloflic acid diisopropYl ester, trif luOrOmethYl biphenyl1>2-carbonyl) amino] phenyl)-acetic acid 2 -pheny1-2,2-biS(2,2,2-trifluoro- ethylcarbaNOYlb-ethYl ester, 2-phenyl-2-(2-{ 4 -trifluoromethYl-biPhenyl-2- carbonyl) -amino) -pheny1}-aCetOXYmflthYl) -malonic acid dimethyl ester, 2-cyclopefltyl- 2 (2-f 4- -trifluorOrfethYl-biPhenYl- 2-carbonyl) -amino] -pheny1)-acetoxy1DethYl) -malonic acid diethyl ester, -trifluorOmfethYl-biPhenY1>2caxbonYl) -amino] phenyll-acetic acid 2,2 ,2-trifluOro-SthY1carbamol)- cyclohexyJIlethYl ester, 2 -phenyl-2 2 4
442-trifuoromethyl-benzoylamino)- pheny1]-aCetoX~YflethY1>-malonic acid diethyl ester, 2-12- (2-phenoxY-benflYaminO) -phenyl] acetoxybethYl2PhenYl-malonic acid diethyl ester, 2-f 2- 2butoxy-beflZOYlamino) -phenyl) acetoxyzethYl2PhenYl-malonic acid diethyl ester, 2-phenyl-2-{ 2 [4-C 2-trifluOrOmelthYl-benzoylocY) en phenyl1-acetOX-Y11IthYl)hmalonic acid diethyl ester, acetor-ymethYlh2-PhenYl-malonic acid diethyl ester, 00 '4 acetoxymethYl)2PhenYl-malonic acid diethyl ester, 0 2 phenyl- 2 -(4(4t[4'trifuoromethyl-biphenyl 2 o carbonyl) -amino] -pheny-) -aceto-yrnethyl) -maloflic acid dicyclohexcYJ ester, -trifluoromethYl4iPhenYl2cabonYl) -ami-no) phenyll-acetic acid 2 2 -bis-cyclohexyJlcarbamoy1-phenYl- ethyl ester, -trifluoromethYlbiphenY1-2-cabonyl) -amino] phenyll-acetic acid 2-phenyl 2, 2 bis phenYlcarbamOY1 -ethyl ester. (4-11(4' -trifluoromethYlbiPhenY1-->cabonYI) -amino] phenyll-acetic acid 2, 2 -bis-isopropylcarbamoyl>2PhenYl- ethyl ester, 2-benzyl-2-(2-{ 4 4 -trifluoronethYlbiPhenYI>2 carbolyl) -amino]I -phenyl) acetoxyinethyl) -maloflic acid diethyl ester, 2-(2-{2-1DethYl'-4-[ 4 y-triflUOrOmethYl-biPhenYl-2- carbonyl) -amino] -phenylJ)-aCetOXYmethYl) -2-pheny-falOflic acid diethyl ester, 41 -trifluoromethYlbiPhenYl2carboxylic acid 4-[2- phenyl-2,2-biS-(2,2, 2-trifluoro-ethYlcarbamoYl) ethoxycarboiylmfethYl] -phenyl ester, biphenyl-2-carbOXYliC acid 4-L2-phefyly-2,2bisi(2,2s> trifluoro-ethylcarbamoyl) -ethoxycarbonylmethYl] -phenyl ester, 2-butoxy-beflzoiC acid 4-[2-phenyl-2,2-bis-(2, 2 2 trifluoro -ethylcarbafoyl) -ethoxycarbolylmfethyl1- phenyl ester, 2-ylhxl2 2f4 4 -rfurmty-ihnl2 00 '4 carbonyl) -amino]I -pheny1}-acetOXymthY))-malonic acid diethyl 0 ester, o4 (biphenyl- 2-carbol) amino -phenyl) -acetic acid 2-phenyl-2,.2-bis- 2,2-trifluorO-ethYlcarbamOYl) -ethyl ester. (2-phenoxy-belzoylalilo) -phenyl]-acetic acid 2- pbhenyl-2, 2-bis- 2-trifluoro-ethylcarbalfyl) -ethyl ester, 2-phenyl-2-(2-(2-trifJluoromethyl- 4 4 trifluoromethyl-biphefll2-CarbofYl) -amino] -phenyll- acetoxymethyl)-malOlic acid diethyl ester, -trifluoromethyl-biphel-2-caIbOflYl) -arino] phenyl)-acetic acid 2-phenyl-2, 2 2-bis -propylcarbamOyl -ethyl ester, -trifluoromethyl-biphel-2-cabOlYl) -amiLno) phenyll-acet-ic acid 2, 2-bis -methylcarbaflY- 2-phefyl ethyl ester, 2-pyridin-2-yl-2-(2-{ 4 -trifluoromethyl-biphelyl- 2-carbonyl) -amino] -phenyl)-acetoxylethYl) -malonic acid diethyl ester, 2-pyridifl-3-Y1- 2 (2-f -trifluoromethyl-biphelyl- 2-carboflyl) -amino] -phenyl)-acetOxylethYl) -malonic acid diethyl ester, 4' -trifluoromethy1-biPheflYl- 2-carboxyJlic acid 4- (2,2- bis-ethylcrbamoflOY2-phel-lethoxcycarbonYlmethyI) -pheny. ester, 0 ~5 trifluoromethYl-biPheflYl- 2 -carbonyl) -amino] -phenyl I- acetoxymethyl)-malOfic acid diethyl ester, 00 2butoxy-belzoyamlfO)-PhenYl] -acetic acid S ~2-phenyl-2. 2-bis- (2,2.2-trif1UOro-ethYcarbaml) -ethyl ester, trifluorOmfethY1-biPhefylY2-CarbonYl) -amfino] phenylli-acetic acid 2,2-bis-butylcarbamoy1-2-phenyl-ethyl ester, 2-2{-(-x-hfurn--abnl-mn] phenyl)-acetOXymlethyl) -2-phenyl-mlalOflic acid diethyl ester, 2-2(-(hfurn--abnl-mn]pey) acetoxymethYl)>2phel>malonic acid diethyl ester, {3-methyl-4- -trifluoromethy1-biPhel-l 2 carbonyl) -amino]I -phenyl)l-acetic acid 2, 2-biLs-ethylCarbamOY- 2-pheflyl-ethyl ester, 2-(-4-(('-ehlbp~y-2croy)-mn phenyl)-BcetoxYmethYl) -2-phenyl-malolic acid diethyl ester, 2-2{-('mtoybpey--abnl-mn] phenyll-acetOXYImethYl) -2-phenyl-malOflic acid diethyl ester, -trifluoromethyl-biPhefl-2-OarbOnYl) -amino] phenyl)-acetic acid 3, 3-bis-ethylcarbalY-3-Phefl>PrOPYl ester, -trifluoromethyl-biPhefylY2-carbOnyl) -amino] phenyll-acetic acid 3-phenyl-3, 3-bis-propylcarbamOYl-PrOPYl ester, [(biphenyJl-2-CarbOfl)-amino] -phenyll-acetic acid 2 ,2-bis-ethylcrbamfl-2-PhelYl-eth~Yl ester, Mr 14- (2-phencxy-beflZOY18minO) -phernyl] -acetic acid 2, 2-bis-ethylcarb8XflY2-PhenYl.ethYl ester, o 5 14- (2-butoxy-belZOYalilO)-phenyl] -acetic acid 2, 2-bis-ethylcarbamol-2-PheflYl-ethYl ester, 00 0' carbonyl) -amino) phenylI-acetOXYmfethYl) -malonic acid diethyl 0 ester, acetoxymethyl)2-Phnfl-lmalonic acid diethyl ester, 4' -trifluoromfethY-biPhefylY12carboxcylic acid 4- bis-ethylcarbafoyl- 2 pheny1-ethOXycarbOflYlmethYl) chioro- phenyl ester, 2-hnl2i-4(-hope--lbnolmn) pheny1]-acetOXyfethY1>.malOnic acid diethyl ester, 2-2[-(ihnl3crbnl-mn]pey) acetoxymethyl) -2-phenyl-malolic acid diethyl ester, 2-(2-{4-[iSOprOpyl-( 4 -trifluoromethy1-biPhenYl-2- carbonyl) -amino] -phenyl}-acetOxylethyl) -2-phenyl-mfaloflic acid diethyl ester, 2- [cyclohexyl- -trifluoromnethy1-biPhefll 2 carbonyl) -amino] -pheny1J'-acetOXYTmethYl) -2-phenyl-malolic acid diethyl ester, 2-2[-2iorplbnolmn)pey] acetoxymethyl>2-phelyl-malonic acid diethyl ester, 2 -(2-t4-(2-benzy-belzoylamliflO)-phenyl]> acetoxymethy1}-2-PhelYl-malonic acid diethyl ester, 2-phenyl-2- -tritluoromethy1-biPhelYl- 2 384 carbonyl) -amino] -pheny1}-aCetoxyn18thYl) -malonic acid dipropyl ester, en 2-phenyl-2-(2-{ 4 1 -trifluoromethY1.biPhenYl-2- carbonyl) -amino]-pey aeoyehl-rnaloriic acid o 5 diisobutyl ester, 2-phenyl-2-( 2 2trifluoromlethoxr-benflnlno) 00 '4 pheny1]-acetOXYmfethY1Th-malonic acid diethyl ester. 0' (2butoxycarbOflbefzlZY1WU))-phenyl] o 8 cetoxmethyl-2-PhenYl-malonic acid diethyl ester, (4-11(4' -trifluoromethYl-biPheny-2-cabofYl) -amitno] phenyll-acetic acid 2 2 -b:isiobUtYCarbamoy1-2-phenyl -ethyl ester, (4-11(4' trifluoromethYl-biPhenfl2-carbonYl) -amino] phenyl)-acetic acid 2, 2-bis- (3-methy1-bUtY1carbamoYiY- 2 pheny1-ethYJl ester, 2- [ethyl-(4-' trifluoromethYl-biPhenYl- 2 carbony-) -amino] -pheny1}-acetOXYmlethYl) -2-pheny-falOfliC acid diethyl ester, (2-cycloh8xy1-benzoylamino) -phenyl] -ac'etic acid 2, 2 -bis-ethylcarbahoy2PhenylethYl ester, 4 b-chlorO..bipheyl12-Carbofl)amiflo1phenYl)- acetic acid 2, 2-bis-ethylCarbamoylOY22Phenyl-ethYl ester, dichloro-biphenfl12-CarbOnYl)-amino] phenyll-acetic acid 2, 2 -bis-ethylcarbamflOY2-Phefl-ethYl ester, 3-methyl-4- -trifluoromfethYl-biPhefyl-l carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2 ,2-bis- propylcarbamlO-ethyl ester, -trifluoromethyl-biphenflY12carbonYl) -amino) 385 CA phenyll-acetic acid 2, 2-bis- (2-methoxy-thYJlcar~bam0Y:) -2- phenyl-ethyl. ester, )-pheny.) -acetoxymethyl] -2- 0 5 pheny.-IfalOfliC acid diethyl ester, [2-methyl-4- (4-trif luorOmfethY1-PhelYl) -thiLazole- 00 '4 5-carboflyl] -axnino)-pheflyl) -acetic acid 2,2-bis- 0 ethyicarbaoyl2-PhenYl-ethYl ester, o (4-f 4 -trifluorOmethy1-PhenY1)-PYridine- 3 carbonyll amino)j- pheflyl) acetic acid 2, 2 -bis -ethy1carbal-l 2-phenyJl-ethY1 ester. (3-methy1-4-[2-(4-trifuoromethY1-PhenYl) -pyridine- 3-carbol) -aminioP-phenyl) -acetic acid 2, 2-bis- ethylcarbamfl-l2-phenyl-ethYl ester, 2-(2-{3-ethy1-4A -trif1UOrOmethY1-biPheflYl- 2 carbonyl) -amino] -pheny1}-aCetOK-Yfl1thYl) -2-pheny1-maOliC acid diethyl ester, {3-isopropyl- 4 -trifluoromelthY1-biPheyl-l 2 carbonyl) amino -phenyl) -acet ic acid 2, 2 -bis -ethylcarbamoyl 2-phenyl-ethYl ester, 2-2 -spoy--('trfurmty-ihnl2 carbonyl) -amino) -pheny11-acetOXYmfethYl) -2-pheny1-ma1Olic acid diethyl ester, (3-ethyl-4- -trifluorOmethyl-biphel-2carbonyl) amnino] -pheny11-acetiC acid 3,3-bis-8thy1CarbamOY1- 3-phenyl-propy)- ester, {3-isobutyl-4- -trifluoromethY1-biphelYl- 2 carbonyl) -amino] -phenyl}-acetic acid 2, 2-bis-ethylcarbamOYl- 2-pheny1-ethYl ester, 386 acddity etr 2-2C-hoo4-(-)ilooety-ihnl2 carbonyl) -amino) -phenyl) -acetoxymethyl) -2-phenyl-mnalonic acid diethyl ester, 2-(2-{3-chloro-4-[ (4'-trifluoronTethy-bipheyl-l 2 carbonyl) -amino] -phenyll-aCtOXYmfethYl) -2-phenyl-maloic acid diethyl ester, 2-(--bronthlO-4-[ (y4' trif-urmethy1-biphefl-bl 2 'y IC) 2carbonyl) -amino]-phenyl) -acetyiety aci 2-phenyl-maloflic acid dibayethyl ester, (3-dinethylcarbalfOyl-4- -trifluoromethyl-biphefyl- 2carbony) -afino -pheylY-acetic acid 2,2-bis-tycraol ethylrbflyl-2ester, hl str {3-dirnethylcarbal'oyl-4- -trif luoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl)-acetiC acid 2,-heny-2-i- roylcarbaioyl-3eYl-l esr, {3({-mehycarbwlcLryl-4- Lifluoroety1biheflY-2 carbonyl) -aio]bonyl-ac]ecacd -bis-xyethylabafl- l 2phenyl-aoi ddethyl ester, 25(3-dietylcarbalfOyl-4- [(4-trifluoromethyl-bipheflYl- 2carbony) -amfio] -pheflY1acetic acid ,-bis-tycraol 2phenyl-lfi ddethyl ester, (3-diinethylcarbafOYl-4- '-trifluoromethyl-biphelyl- 2-carbofl)-aXTilo]-phefylY1acetic acid 4,4-bis- ethylcarbafoyl- 4-phenyl--bUtyl ester, {3'-diethylcarbafoYl- 4 -trifluoromethyl-biPhelYl- en 2-carbofyl)-amilO>-PhenY1Thaoetic acid 2,2-bis- ethylcarbamfoyl- 2-phenyl -ethyl ester, o {3-diisopropylcarbafOYl> 4 -trituoromlethy'1- biphenyl-2-CarbOlyl) -amino] -phenyl)-aCetic acid 2,2-bis- ethylcarbamOYl2phefllethYl ester, 2- (2-{3-diethy-CarbamfOYl-44 -trifluoromethy- o biphenyl-2-CarbOlYl) -amino] -pheny1}-8cetOXYmethYl)- 2 phenyl-mfalofliC acid diethyl ester, 2- 3-diisopropY1CarbaflnOYl- 4 -trifluoromethyl- biphenyl- 2-carbonyl) -amino] -phenyl}-aCetox-YmfethYl) -2 -phenyl- malonic acid diethyl ester. (isopropyl-methYl-CarbalOYl) trifluorOmethYl-biphelYl-2-carbonYl) -amino] -phenyll- acetic acid 2,2-bis- ethylcarbatiOyl 2-phenyl-ethy. ester, 2-(2-{3-(ethyl-methyl-Carbamoyl- 4 trifluoromethYl-biPhefll2-carbonYl) -amino] -phenyli- acetoxymethyl)2-Phel-lmalonic acid diethyl ester, (ethyl-methyl-carbfloYl) -trifluorornethyl- biphenyl-2-CarbOlYl) -amino) -phenyll-acetic acid 2 ,2-bis- ethylcarbamoyl2-PhelYl-SthYl ester, (ethyl-methyl-carbafOYl) -trifluoroinethyl- biphenhyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 3, 3-bis- ethylcarbamOYl-3-PheflProPYl ester, (piperidine-1-CarbOlYl) -4-f -trifluorcnnethyl- bipheny1-2-carboflyl)-amiflOh.phenYl)-acetic acid 2, 2-bis- ethylCarbamfoyl- 2 -phenyl-ethyl ester, 388 (pyrro11difel1-cazruonYJ 4-(4 -trif luOrOmfethYl- bipheny1-2-carboflYl) -amino] -phenyl) -acetic acid 2, 2-bis- en ethylcarbamOyl> 2 phen1T1-etbYJl ester, 00 (pyoidifl-Crbo~Yl) [(4'trifuOrOmfethYl- 0 biphenyl-2-CarbOlYl) -ajino]-phenflTaCetic acid 2, 2-bis- ethylcarbamOyl 2-phenyl-ethyl ester, (rethy1-propy1-CarbamotI) -trif1uorOmethYl- 0 biphenyl-2-CarbOlYl) -amino] phenyI)-aCetiC acid 2 ,2-bis- oethylcabamOYl23PhenYl-ethYl ester, (3-dimethy1CarbamOYl- 4 -trifluorOffethY-biPhenYI- 2-carboflyl) -amino] -pheny1)-aCetic acid 2-ethylcarbazuOYl- 2-phenyl-etbYl ester, 2 -phenyl 2 (2(3ipyrrodnelcarbony)4[(4 trifluoromethYl-biphenY> 2 -carbony))-amino] -pheflyl) acetoxymfethYl)-malolic acid diethyl ester, 2-hnl2(-3(ieldn--abnl--(1 trifluorOtfethYlbiPheny> 2 -carbony)- amino] -phenyll acetoxyflethYlh-malonic acid diethyl ester, {3-dimethy1carbamtoyl- 4 '-trifluotomethY1-biPhenYl- 2-carbonyl) -amino] -pheny1}-acetiC acid 2-pheflyl-2- propionylamino-ethYl ester. (3-dimethylcarbamoyl- 4 -trifluorOTmethYl-biPhenYl- 2-carbon))-amino] -pheny3-1-aCetic acid 2-phefyl-2- propionylamfino-ethyl ester, (3-dimethYlcarbamOYl-4-[(4' -trifluorOflethYl-biPhenYl- 2 -carbofl)-amfiolO>Phenyl-acetic acid 2-(2,5-diOXO' 389 pyrrolidinu 1 -2-pheflyl-SthYl ester, {3-dimethylCarbX1OYl- 4 t -trif lUorOmethYl-b±PhenYl- m2-carbol) -amino] -phenYJl)-aCetiC acid 2-ethylCarbamolO- benzyl ester, o 5 {3-dimethylCarbamoyl- 4 -trif luoromethYl-blPhenYl> 2-carboflyl) -amino] -phenyl) -acetic acid 2- 00 ethylcarbafOYlmethYl-beflzYl ester, 3 dimethYlcarbamoy- 4 -trifluoromethYl-biPhenYi- ci 2-carboflyl) -amino] -phenyl) -acetic acid 2-isoProPYlalUfO- 2 phenyl-ethYl ester hydrochloride, [3dmthlabaol4(2-triflUOrOmfethYl- benzoYlaTinfO) -pheflyl] -acetic acid 2, 2-bis-ethYlCarbam'oy'- phenyl-ethYl ester, [3-dimethylc-rbamfOYl- 4 -(2-triflUorOmethYl- benzoyalU-o) -pheflyl] acetoxymethYl 2PhenYl-maloaic acid diethyl ester, 2 2 2 3 -dinethylcarbaoylOY>[44(4tflrfotyl bipheny1-2-carbOflVamino] -phenyl1-aCetoxY) -ethyl] -2- phenyl-malOflic acid diethyl ester, 2-2(-intycraol--(1fur-ihnl2 carbonyl) -amino] -phefl1}acetoxWmethYl) -2-pheflyl-falOfliC acid diethyl ester, 2-2{-(1boobpey--abnl-mnj3 dimethylcarbafol-PhenYl-acetoxmethyl) -2-phelyl-flofliC acid diethyl ester, (3-dimethylcarbamOYl- 4 -trifluorOmethYl-biPhenYl- 2-carboflyl) -amino] -phenl)-acetic acid 2-acetylamifo-2 phenyJ.-ethyl ester. {3-dimethylcarbamoyl- 4 -trifluorOmfethYlbiPhefl 2-carbol) -amino] -phenyl) -acetic acid 2-bUtYrY18ThifO-2 phenyl-ethyl ester, en [4-C 2-berxzoy1-beflZOYlamino) -3-dimethy1CarbamOYl- phenyll-acetic acid 2 2 -biS-ethYlcarbamoY1>2PhenYi-ethYl o 5 ester, 4 -(2-beflZOYlbelzoylamino) -3-dimethYlcarbamoYl- 00 '4 phenyl] -acetoxymfethYl-2PhenYi-malonic acid diethyl ester, 0) Z-{3-dimethylcarbamoYl- 4 -trif1UOrOmethYl- ci biphenyl-2-CarbonYl) -amino] -pheny1)-aCetOX-YITethYl) -2- phenyl-mlaloflic acid dilnethYl ester, trifluoromethYlbiPhenYl-2cabonYl) -amino] -pheflyll-aCetoxy methy)-falofiC acid diethyl ester, 2 -cyclohexy-2(2d(3aimethYlcarbamoy- 4 trifluoroffethY-biPhenY1-2-cabonyl)-aio-hnl-ctx methyl)-mfalonlic acid diethyl ester. 2 2 4 4 l-chloro-biphenY-2-carbol)amn]3 dimethYlcarbamOyl-PhenYl) -acetoxymethYl) -2 -pheny-la1Oflic acid diethyl ester, 2 2 44 4 -acetybiphenY122carboy)-n1]- dimethYlcarbamoYl-PhenYll -acetcncyiethYl) -2 -pheny-fl1Oflic acid diethyl ester, I[3-direthy1CarbamOYl 4- (2-pher1OXY-beflZOYlamin~o) phenyll-acetic. acid 2. 2 -bis-ethYlcarbamOY-2-phenYl-ethyl ester, 2-12- [3-dimethylcarbamOYl- 4 (2-phenoXY-beflZOYlamino) phenyl] -acetoxyrethY1-2-phenlmalonic acid diethyl ester, 2 2 4 4 cyanobiphenY-2carbolanY1l- dimethylcarbaXOoy1-phenyl)hacetoxymethyl) -2-phenY1-mfa1oflic acid diethyl ester, 2-2(-:mtylabmy-- (4-methyl-A'- en trifluorOffethYl-biPhenyl2cabonyl) -amino] -phenyl) acetoxymethyl) -2-phenyl-malOflic acid diethyl ester, 2 2 -(3-dimfethylcarbolOY4[(5methyl> 4 trifluorOmethYl-biPhenYl-caboflYl) -amino] -phenyl)- 00 '4acetoxymethyl-2-Phelmalonic acid diethyl ester, 0' (3-dirnethYlCrbal- 4 trifluoroflethYlbiPhelYl- o 2-carboflyl) -amino] -phenyl)-acetic acid 2- methanesulfOfYlamilO-2phenYl-ethYl ester, 3- (2-t3-dirnethYJ-CarbamfOYl- 4 -trifluorc'methyl- biphenyl-2-CarbOlYl) -amino] -phenylll-acetoxy) -2-phenyl- propionic acid ethyl ester, (3-dimethylCarb1flY 4 -trifluoromethY1-biPhenYl> 2-carboflYl) -amino] -phenyll-acetic acid 2- (methyl-propiOlYl amino)-2-pheflYl-ethyl ester,- (2-{3-dimethylCarbamOYl- 4 -trifluoroinethYl- biphenyl-2-CarbOlYl) -amino] -phenyl)-aCetOXY) -propyll -2- phenyl-faloflic acid diethyl ester, 2 2 -(3-dimethylcarbamoy-4[(5-methoxy- 4 trifluorOmfethYl-biPhenYl2carbonYl) -amino I-phenyll acetoxymethylV2-PhenYl-malonic acid diethyl. ester. 2- (2-114-1 (5-chlor'-4' -trifluorOtflthyl-biPhenYI- 2 carbonyl) -amino] -3 -dimethylcarbamOYl -phenyl) acetoxyrethYlv2-PhenYl.maxonic acid diethyl ester. 2 -(2-(3-dimethYlCarbamoYl- 4 -[(6-methyl-4C- trifluororfethYl-biPhenYl-2-carbonYl) -amino) -phenyl) .acetoxymethYl)2-PhenYl-malonic acid diethyl ester) 2-(3-dimethYlcarbamOyl- 4 1(4' -trifluorofethyl- 392 biphenyl-2-CarbOflYl) -amino] -pheny1J-aCetoxymethYl) -2- phenyl-maloflic acid di-2, 2, 2-trif1UOrOethY1 ester. 2 2 -(3-diethleharboy4(2fluoro- 4 trifluorOmfethYlbiphenYl 2-carboflyl) -amino] -phenyl) acetoxmethYlh-2phenyl-malonic acid diethyl ester, 2 2 -{5-dimethy1Carb8IDoy2fJloro 4 4 l. 00 '4 trifluorOmethYl-biphenYl 2-carbonyl) -amino] -phenyl) 0' acetoxyrnethyl) -2 -phenyl-mfalonic acid diethyl ester. trifluoromethYl-biPhenyl-2-carbonyl) -amino] -phenyl)- acetoxymethyl) -2 -phenyl-a-lOfliC acid diethyl ester, 2 2 3 -ch1oro-5-dimethylcarbamoy1- 4 4 trifluoromethyl-biphenYl 2-carboflyl) -amino] -phenyl) acetoxymethYlh-2phenyl-malonic acid diethyl ester, 2 2 -(3-dimethy1carbamoy1-4-(3fluoro- 4 trifluoromethY2lThiPhenY1-2carbonYl) -amino] -phenyl) acetoxymethyl) -2-pheny1-malOfliC acid diethyl ester. 2- -chloro-4' -trifluorOmfethYl-biPhen~yl- 2 carbonyl) -amino] -3 -dimethylc8arbW1oy1-PhenYl) acetoxymethY1)-2-phenY1Wmalonic acid diethyl ester, 2- 2-{3dimethycarbarfloyl- 4 -trifluoromfethY1- biphenyl-2-CarbOflYl) -amino) -pheny1)-acetoxymflthYl) nitro-pyridin2-Yl) -malonic acid diethyl ester, 4- -trifluorOmthYl-biPhenYl-2carbonYl) -amino] -phenyl I- acetoxymethyl)-malonic acid diethyl ester, 2- 2{3-dimethy).carbamoyl-' 4 -trifluoromfethyl- biphenyl- 2-carbonyl) -amino] -phenyl) -acetoxyniethyl) -2- pyridin-2-Yflmalonic acid diethyl ester, 393 2 -carbonyl) -amino ii-phenyl 1- enacetoxymethYlV-2phenyl-malonic acid diethyl ester, 00 o btifhl-lehl-hnl 2 -carbonyl) -amino] -phenylI-ctxmtyl) -2 o atoxehhheymalonic acid diethyl ester, 102- (2-{3-dimTethY1CarbamoYl- 4 -trifluorOITethYl- o ~biphenyl-2-CarbOlYl) -amino] -pheny1}-aCtOXYmflthYI) tolyl-malolic acid diethyl ester, 2- (2-{3-dimethY1CarbamOYl- 4 -triffloromethYl> biphenyl-2-CarbOlYl) -amino] -pheny)-aCtOXYfltthYl) -2 -i- tolyl-malotic acid diethyl ester, 2- (2-c(3ordimeY1Carba2-o3l 4 ytrifiuofl-4thY> tiloehbiphenyl-2-Caball)-mio bohny)-ametoXpmehYl) -p toymi-ofl)-ic acid diethyl ster, 2 2 -chloro-phefylY)22(3dimethylcarbamoyl 4 [(41 2 -carbonyl) -amino] -phenyl) acetoxymethYl)-malonic acid diethyl ester, 3-chioro-Phelyl) (2-{3-dimethY3lcarbam0Yl- 4- trifluoromethYl-biPhenYl- 2 -carbonyl) -amino] -phenyl) acetox-ymethyl)-malonic acid diethyl- ester, tiflohlihenyl-2carbonl) -amino] -phenyl)-actxmty)2 phenyl-succilic acid diethyl ester, 2- (2-{3-dimethY1CarbamOYl- 4 -trifluoromethY1- biphenyl-2-carboflYl) -amino] -pheny1)-aCetoxymfethYl) -2-C 2- methoxy-pheflYl)-malonic acid diethyl ester, 5'2- 2(3-di-methyJ-carbSmofl- 4 -trifiuor)IfethyJ- en biphenyl-2-CarbOlYl) -amino] I phenyl1-aCetOX-YImlthYl) 2- (3- methoxy-pheE1Yl)-malOnic acid diethyl ester, biphenyl2Cr) J)-amino t heflrmyl-acetnYmehl)-- 4 10metox-ymePhflY12phemalonic acid diethyl ester 'fl 2- [(5,41 rbis'trifluorOmethY-biPhenY~-2 o carbonyl) -amino] -3-dirnethy1CarbamoYJl-PhenYl)> 10acetoxymethy1)-2-Phefl-malonic acid diethyl ester. (echylorb4?otrifU-r(m6thYbirhen4l- ca rbloyl -mino] 3ietyl2carb8Tonyl-heno])-pny) acetoxymetlyl) -2 -phenyl-m2LOfliC acid diethyl ester, -amino] -phenyll- acetoxym-ethyl)2-PhenYl-malonic acid diethyl ester, 202-12- (23dimethYlcarbamOYl- 4 -[(5-ethy-4' trifluoromethylmbiPhenYl-2-carbonYl) -amino] -phenyll acetoxy) ethyl] -2phenyl-IfalOfiC acid diethyl ester, 2 2 3 -dimethylcarbamoylO-4(5ethoprpoy-4 4 trifluoromethYl-biPhenYl>2cabonYl) -amino -phenyl)- acetoxymethYl)2-PhenYl-malonic acid diethyl ester, 2 (5, 4 t-biS-trif1uoromethYl-biPhenYl- 2 carbonyl) -amino] 3 -dimethylcarbamolYPhefl)l-acetoxy) ethy1]-2-pheflYl-malonic acid diethyl ester, 2 -(2-{3-dimethYlcarbamoYl- 4 (6-rnethOXy-4' trifluOrOffithY1-bPheny1-2cabonYl) -amino I-phenyl) acetox-yrethyl) -2-phefl-ma1OfliC acid diethyl ester, 2 2 3 dimethy1carbamoylOY4-(3-methyl-4' trifluoromethYl-biPhenyl- 2 -carbony-) -amino] -phenyll o 5 acetoxymethY1)-2-PhenYl-malonic acid diethyl ester. 4 -bis-trifluOrOmfethYl-benzoYlahino) -3- 00 dimethylCarbamIl-PhenYl] -acetoxymethyl) -2 -phenyl-faJliC 0 acid diethyl ester, o 2 -(2-(3-dimethYlCarbamlY- 4 -methyl-biphenfl 2 carbonyl) -ami-no] -pheny1)-aCetOSYImethYl) -2-phelbTm1OliC acid diethyl ester, 2 -ethYl-4-triflUOromethYl-belzoylamino) -phenyl 3- acetoxymethY1Y-2-P1enyl-malonic acid diethyl ester, 2 -(2-(3-dJSmethYlC8arb8IoYl- 4 '-ethyl-biphefl2- carboniyl) -amino) -phenyl)-aCetOXYmfethYl) -2-pheny-falOfliC acid diethyl ester, 2 -(2-{3-dimethylcarbamoyl"4 -isopropeflyl- biphenyl-2-CarbOlYl) -amino) -phenyI)-aCetOXYI11thYl) -2- phenyl-mialoflic acid diethyl- ester, 2- (2-(3-dimethYlCarbamoyl' 4 -isopropyl-biPhelYl- 2-carboflyl) -amino] -pheflyl)-aCetO2WyrnethYl) -2-phefl-fa1liC acid diethyl- ester, (3-dimethylCarbafloyl- 4 (2-i-soprOpelYl- 4 trifjluorotfethYl-benzoYlamino) -phenyl J-acetoxyiethYl> 2 phenylIfalofliC acid diethyl ester, 2 2 -[3-dimethylcarbamoy-4-(2-isopropyl-4 trifluorOmethYl-benzoylamino) -phenyl] -acetoxytethyl>- 2 phenyl-faloflic acid diethyl ester, 2- (2-(3-dimethylcarbamIoyl- 4 12- (3-triflUOrOmfethYl- 396 phenylamilo -benzoylamifl]phenyi}-aCetOXYrflthYl) -2 -phenyl- malonic acid diethyl ester, en dimnethylcarball-4- trif luoromethyl bipheny1-2-CarbOflYl))-phenyl] -acetoxymethy1-2-PhenYl- malonic acid diethyl ester, 2-(-3dntycraol4 -(-rflooehl 00 phenosy) -benzoylamifl0] pheny1)-aCtOXYmfethYl) -2-phenyl- malonic acid diethyl ester. o -dimethy1Carbamoyl- 4 -trifluorOmr)thY1-biPhenYl- 2-carbonyl) -amino] -phenyl)-acetic acid 2-ethy1-2-phnlY)- buty- ester, 2- (2-{3-difl1thYCarbaDIoyl 4 (4-trifluoromfethYl- phenoxy) -ben zylafilo] -phenyll -acetoxyniethyl) -2 -phenyl- malonic acid diethyl ester, (3 -dimnethylcarbamfoYl- 4- -trifluoroniethYl-biPhenYl- 2-carbonyl) -amino] -phenyll-acetiC acid 1-phenyl- cyciopropylmethyl ester, {3-disnethyicarbalOYl- 4 -trifiuoromethyl-biPhell 2-carboflyl) -amino] -phenyll-acetic acid 2, 2-diphenyl-ethYl ester, (3-dimethyicarbwfolO~- 4 [(4'-.trifluOrorflthY1-biPhefli- 2-carbol) -amino] -pheny]-)-acetic acid 1-phenyl- cyciopentyimethyl ester, (3-dimethylcarbamOYi- 4 -trifluoroinethy1-biPhel- 2-carbony))-amino) -pheny1}-acetic acid 3-hydroxy-2- hydroxymethrl- 2-phenyl-propyl ester, 3-dimethy1carbamoyi- 4 -trifluoromethyi-biPhenfli- 2-carbol))-amino] -pheny1}-ac'etic acid 3-acetoxy-2- acetoxymethYl>2PhenYl-ProPYi ester, 2-(3-di~methy1CarbaflOYl- 4 -trif1luorOmflthY1- (1)biphenyl-2-carbonYl) -amino] -pheny1}-aCetoxyIUethYl) -2- thiophefl-2-ylma1OliC acid diethyl ester, 2- 2-(3-dimethYJCarbamOYl' 4 ((4'-trif luorOmethyl- biphenyl-2-CarbOlYl) -amino] I pheny1)-aCetOX-ymfethYl) 2- thiophefl-3-Y1-ma1Oflic. acid diethyl ester, 00 '4 2- (2-{4-dimethy1Carbamfoyl--[(4' -tritluorcmethyl- 0 biphenyl-2-CarbOlYl) -amino] pyridin2-Y1}-acetox-YmethYl) -2- o phenyl-falOflic acid diethyl ester, 2- (2-{3-dinmethY1Carbamfl- 4 -trif luoromfethyl- biphenyl-2-Carbol)-amino] -pheny1)-acetoxymethYl) (3- methyl-thiophefl 2 -malonic acid diethyl ester, 2- (2-(3-ditflthy1Carb8ThOYl- 4 -trifluorOmfethyl- biphenyl-2-CarbOlYl) -amino) -pheny1}-aCetOXYmfethYl) methy1-thiOPhefl2-Yl)-maloni~c acid diethyl ester, 2- {3 -dimethylcarbamfoYl- 4 triluoromethyl biphenyl-2-CarbOlYl) -amino] -phen-Kl)-acetOXYmethYl) -2- thiazo1-2-y1-malOliC acid diethyl ester, 2- 2-{3dilethy1CarbIl- 4 -L -trifluoromfethyl- biphenyl-2-CarbOlYl) -amino] -pheny1}-aCetoxyflethYI) -2- isopropyl-malolic acid diethyl- ester, 2-sec-bUtyl- 2 (2-{3-dimethylcarbIfl- 4 trifluoromethyl-biphel-2 -carbonyl) -amino] -phenyl 1- acetoxymethyl)-malolic acid diethyl ester, 2- (2-{3-dimethylcarbafl- 4 -tnifluorofethyl- biphenyl-2-CarboflYl) -amino) -pheny1)-aCeto2CYmfethYl) -2- isobutyl-malolic acid diethyl ester, 2- (2-{3-dimethylcarbamfoYl- 4 -trifluoromfethyl- biphenyl-2-CarbOlYl) -amino] .pheny1}-acetoXYmfethY))-2- 398 propyl-an&Lic acid diethyl ester, 2- (2-{3-dimethYlcarbamQYl- 4 -trifluorOmfethYl- en biphenyl-2-CarbOlYl) -amino] -pheny11-aCetOXYmflthYl) -2 -ethyl- malonic acid diethyl ester, trifluorOmetbYl-biPhenY1-2-carbonyl) -amino] -phenyl) acetoxymetyliflalolic acid diethyl ester, 0 2 allyl2(2(3dimethylcarbamoyl 4 4 o trifluorOmethYl-biPhenY1>2carbonYl) -amino] -phenyll- acetoxymethyl)-maloniLc acid dielthyl ester, a-(2-{3-dimethYlcarbamoYl- 4 -trifJluOrOmfethYl- biphenyl-2-CarbolYl) -amino] -phenyl)-acetOXY) 2-bis- ethoxycarbOfllPropiOnic acid ethyl ester, 2-{3-dimethYlCarbamOYl'4-[(4' -triflUOrOmethY1' biphenyl-2-CarbOflYl) -amino] -pheny1)-acetOXYmfethYl) 1- methyl-bUtYl)-malOnic acid diethyl ester, 2-2(-toy4[4-rfurmty-ihnl2 carbonyl) -amino] ,-phenyl) -acetoxymethyl) -2 -phenyl-falOfliC acid diethyl ester, {3-hydroxy-4- -trifluoromethYlbiPhenYl-2- carbonyl) amino -phenyl)l-acetic acid 2, 2 -bi-s-ethYlCarbamOYl- 2-phenyl-ethyl ester, {3-methOXy- 4 -trifluorOmfethYlbiPhnyl>2 carbonyl) amino I -phenyl)- aCet ic acid 2, 2 -bis -ethylCarbamOyl 2-phenyl-ethYl ester, 2-(2-t3-metho2Cy- 4 -trifluoromfethYl-biPhenyl- 2 carbonyl) -amino] -phenyl}-aCetOXY11ethYl) -2-phenyl-falOfiC acid diethyl ester, {3-methoxy- 4 -trifluoromfethYl-biPhenyl>2 399 carbonyl) -amino)I -phenyl)l-acetic acid 2-phenyl-2,2-biS- propylcarbamfOy-ethYl ester, en {3-methOXy-4- -trifluOromethYl-biPhenYl- 2 carbonyl) amino]j -phenyl)- acetic acid 3, 3 -bis -ethylcarbalY- o 5 3-phenyl-prOPYl ester, {3-ethoxy-4- -trifluoromethYJ.-biPhenYl- 2 00 '4carbonyl') amino] phenyl)l-acetic acid 2, 2 -bis -ethYlcrbafl 0) 2-pbhenyl-ethYl ester, o ~{3-ethoxy-4- -trifluoromethY1-biPhelYl- 2 carbonyl) amino]) -phenyl) -acetic acid 3, 3 -bis -ethylcarbamoYl- 3 -phenyl-prOpyl ester, 2- (2-{3-iSOprOpoxr-4 -trifluorO~fethy1-biPhenYl-Z- carbonyl) -amino) -pheny1)-acetOXYflethYl) -2-phenyl-mfalOfliC acid diethyl ester, (3-isopropOXY- 4 -trifluorOmlethYl-biPhenYl 2- carbonyl) -amino] -phenyl)-acetiC acid 2, 2-bis-ethyCarbalY- 2-phenyl-ethYl ester, (3-isopropOxY- 4 -trifluOrOmethY1'biPhenYl 2- carborlyl) amino]I -phenyl)l- acet ic. acid 3, 3 -bis -ethyCarbamyl- 3-phenyl-prOPYl ester, {3-propoxy-4- -trifJ-uOromethY1-biPhel- 2 carbonyl) -amino] -phenyJ-)-acetic acid 2, 2-bis-ethylcarbamOYl- 2-phenyl-etb.Y1 ester, {3-benzyJ.OXy-4- -trifluoronmethy1-biphenfl-l> carbonyl) -amino] -phenyl}-acetiC acid 2, 2-bis-ethy1CarbW11OY1- 2-phenyl-ethyl ester, 2- (2-(3-beflzylOxy- 4 -triiluorOrfethY1-biPheflYl-2- carbonyl) -amino] -pheny-) -acetoxymethyl) -2-phenyl-ma-OfiC acid diethyl ester, 400 (N 2-(2-{3-hydrOXY-4- -trifluoromfethY1TiPhnYl 2 carbony)--amino] -phenyl) -acetoxyniethyl) -2 -pheny1-fla1liC acid diethyl ester, [3-methoxy-41 4 1-trifluoromnethY-biPhenYl- 2 0 5 carbonyloXY) -phenyl] acetoryrethY1Th2-PhnYlnilofic acid diethyl ester, 00 (3-dumethylafifo- 4 -trifluoromethYl-bJPhenY> 2 VC) carbonyl) -amino)I -phenyl)- acetic acid 2, 2-bis-ethy1CarbamOYl- o 2-phenyl-ethYl ester, (3-piperidifl-1-Yl- 4 -trifluorOmethYl-biPhenYl- 2 carbonyl) -amino]I -phenyll -acetic acid 2, 2-biS-ethY1CarbamOYl' 2-pheny1-ethY1 ester, (3-pyrrOlidir-lYl- 4 -trifluoromfethy1-biPhenYl' 2 carbonyl) -amino] -phenyl)- acetic acid 2, 2-bis-ethYJlcarbamOYl- 2-phenyJl-ethY1 ester, 2 -pheny1-2(23piperdn1-y'4-[( 4 trifluorOmethYlbiphenYl-2carbonYl) -amino] -phenyl)- acetoxymfethYl)-lfalonxo acid diethyl ester, 2 -pheny1-2(23PYrrOlidin1Yl> 4 triLfluoromethYl-biphenYl-2carbonYl) minoI -phenyl)- acetoxymethyl)-malonic acid diethyl ester, 2- (2-{3-dimthylam ino-4- -trifluoroflethYl- biphenyl-2-CarbOlYl) -amino]-~pheny1}-acetOXYmnethYl) -2- phenyl-faloflic acid diethyl ester, 2- (2-{3-morphOlif-4-Yl- 4 -[(4'-~trifluorOmfethY3l-biPhenY 1-2-carbolyl) -amino] -pheny1}-aCetOXYmfethYl) -2-phenyl- malonic acid diethyl ester, 2- 3-diethylafiflO- 4 -trifluoromethY1-biPhenYI- 2-carbonyl) -amino] -pbeny1)-aCetO2CYflethYl) -2-pheny-Ta1OfliC 401 0 acid diethyl ester, C)22(2 2 methy--(4-til3[(4mtylbphnl2 carbonyl) -anino-phenyl)-aCetOXY) -ethyl] -2-phenyl-laloflic Ci acid diethyl ester, 2-phenyl-2-( 2 3 -[(4'-triflUorDmlethYl-bPhenYl- 2 carbonyl) amino] phenyl)- aCetOXYflethYl) -malonic. acid diethyl 00 ester, o carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -malonic acid diethyl- ester, -trifluoromethy1-bipheflYl-2'cabOfYl) -amino] phenyl)-acetic acid' 3, 3-bis-ethylcarbaflOYl-3-Phel3-ProPYl ester, -trifluoromethyl-biphel-l2-CabolYl)-am-ino] phenyll-acetic acid 3-phenyl-3. 3-bis-prOpylCarbalY-PrOPYl ester, 2-2(-4mty--(1trfurmty-ihnl2 carbonyl) -amino] -pheflyl)-acetoxy) -ethyl] -2-phenyl-ialolic acid diethyl ester, 2-2(-2mty--('trfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-malonic acid diethyl ester, -trifluoromethyl-biphenYl-2-'CabonYl) -amino] phenyiji-acetic acid 3, 3-bis-isopropylCarbamfOYl-3-Phel- propyl ester, (2-methyl-3- -trifluoromethyl-biPhenYl- 2 carbonyl) -amino]I -phenyl) -acetic acid 3, 3-bis -ethylCarbafloyl- 3 -phenyl-prOpyl ester, (2-inethyl-3- -trifluoromethyl-bipheflYl- 2 carbonyl) -amino] -phenyl) -acetic acid 4, 4 -bis -ethylcarbafoyl- C) 4-phenyl-butyl ester, {2-methyl-3- -trifluoromethy-biph8Yl 2 carbonyl)-amilO]-phenyll-acetic acid 3-phenyl-3,3-biS- propylcarbamoyl-PrOPYX ester, f2-methoxy-3- -trifluoromethyl -biphefll 2 carbonyl) amino] -phenyl) acetic acid 3, 3 -bis -ethylcarbamoyl- Vn 3-phenyl-propyl ester, o 2-[2-(2-{2-methOxy-3-[ (4'-trifluoromethyl-biphelyl-2- carbonyl) -amino] -phenyl}-acetOxy) -ethyl] -2-phenyl-malonic acid diethyl ester, (2-ethoxy-3- -trifluoroinethyl-biPheflYl-2- carbonyl) -amino -phenyl)l-acetic acid 3, 3 -bis -ethylcarbafoyl 3-phenyl-propyl ester, 2-[2-(2-{2-ethOXY-3-[ (4'-trifluorofethyl-bipheflyl-2- carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-nalonic acid diethyl ester, 2-2(-2iorpx--('tllooehl biphenyl-2-carbOInYl) -amino] -phenyll-acetoxy) -ethyl] -2- phenyl-rnaJonic acid diethyl ester, 2-[2-(2-{2-methoxycarbOlYl-3-t (4'-trifluoromethyl- biphenyl- 2-carbonyl) -amino] -phenyl) -acetoxy) -ethyl] -2- phenyl-nialonic acid diethyl ester, 2-2(-2ehx--ehl--('tilooehl biphenyl-2-carbolyl) -ami-no] -phenyll-acetoxy) -ethyl]-2- pherxyl-nlalOflic acid dietbyl ester, -trifluoromethyl-biphelyl-2-crbOlyl) -amino]- benzoic acid 2- [9-(2,2,2-trifluoro-ethylcarbal)-9h- fluoren-9-yl] -ethyl ester, Cl -tritluoromethy1-biphefl2-C&bOflYl) -amino] benzoic. acid 2-(gh-fluorefl-9-yl)-ethYl ester, n-biphenyl-2-yl-terePhthal aTiC acid ,2- trifluoro-etylcarbmoYlP9h-t1UOren-9-Yl]-ethyl ester, -trifluoromethyl-bipheflYl-2CabonYl) -amino] benzoic. acid 2- ((biphenyl-2-CarbOlYl)-amino) -ethyl ester, 00 4- -trifluoromethyl-biphelyl-2-CabOfYl) -amino] tfl benzoic acid 2-A2-.bipheny1-2-Yl-aCetYlailo) -ethyl ester, o 4- -trifluoromethyl-bipheflyl-2-c5XbOfYl) -amino] benzoic acid 3-naphthalen1yl-3-(2,2,2-triflUOro- ethylcarbanoyl) -propyl ester, 4- '-trifluoromethyJl-bipheflyl-2-CarboflYl) -amino] benzoic acid 3-12- 2-trifluoro-ethycarbaloyl) naphthalen-1-yl] -propyl ester, -trifluoromethyl-biphelyl-2-CarbolYl) -amino] benzoic. acid 3,3-diphenyl-3-(2,2,2-triflUoro- ethylcarbamoyl) -propyl ester, 4- -trifluoromethyl-biphenyl-2-carbOnYl) -amino] benzoic acid 3-biphenyl-2-yl-3-(2,2,2-trifluoro- ethylcarbamoylj-propyl ester, 4- -trfluoromethyl-biphefl-2-CarbOnYl) -amino] benzoic acid 3-phenyl-3-(2, 2,2-trifluoro-ethylcarbamioYl) propyl ester, 4- -trifluoromethyl-bipheflYl-2-carbOlYl) -amino] benzoic acid 2-18- 2-trifluoro-ethylcarbfloYl) naphthaen-1-yIl]-ethyl ester, -trifluororethyl-bipheflyl-2-carbOlyl) -amino] benzoic acid 3-(2,6-dichloro-pheflyl)-3-(21 2,2-trifllorO' ethylcarbam~oyl) -propyl ester, (N -trifluoromethy1-biphenfl-2-CabolYl) -amino] C)benzoic acid 3-2clr-hnl--222tiloo ethylcarbafoyl)-PrOPYl ester, 2-phenyl-2-(2-{ 4 -E( 4 -trifluoromethY1-biphelJ2- carbony1)-amfiflo]bnfolYoxy)ethYlh-malonic acid diethyl IC) ester, 00 2-2f-ehl4[4-rfurmty-ihnl2 In carbonyl) -amino] -beazoyloxyl-ethyl)-2-phenyl-malolic acid o diethyl- ester, -trifluoromethy1-biPhefl-2- carbonylo) mn-benzoyloxyl-ethyl) -2-heyaofic acid dehletr peymaiacddiethyl ester, 2-phny-2{4-('-trifluoromethyl-biphnhefcrbnl)- 2 m- phenyliafic acid iethlabmy--hnlpoyl ester, 4. -trifluoromethy1-biphel-2 -carboxylic acid 3 -bis-ethylcarb8IUOy1-3-Phefl1PrOPOXYcarbonYl) -2- chloro-pheflyl ester, 4' -trifluotomethy1-biPhenfl-2-CarbO2Wlic acid 4- (3,3bsehlabaol3pey-pooyabnl-phenyl ester, 4' -trifluoroinethyl-biphefl>2-carboxylic acid 4-(3 ,3-bis-ethylcarbamoy1-3-Phenfl-PrOPOXYcarbOnYl) -2,6- dichioro-phelyl ester, 4-methyl-4- 1(4' -trifluoromethy-biPhel-2-CarbOflYl) amino] -cyclohexanecarbOxylic acid 2- 2-trifluoro- 405 ethylcarbamoyl) -9h-fluoren-9-Y1] -ethyl es~ter, 4- -trifluoromethY1-biPhefl2-CarbonYl) -antino] cyclohexanecarbOxYlic acid 2- (2.2,2-trifluorO- ethylcarbaloyl) -9h-fluoren-9-yl) -ethyl ester, 4- -trifluoromethy-biPheflYl-2-CarbOfYl) -a-mino] cyclohextafecarbOxyliC acid 3-pbenyl-3- 2-trifluoro- 00 ethylcarbamfoYl)-prOPYl ester, V')2-phenyl-2-(4- -trifluoromethyl-biPhelYl- 2 o ~carbonyl) -amino] -cyclohexanecarboflOXYmfethYl} -malonic acid diethyl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) -amino I-cyclohexanecarbolyloxy) -ethyl) -malonic acid diethyl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) -amino) -piperiin--yI1-acetoxflhethyl) -malonic, acid diethyl ester, 2-phenyl-2-(2-( 4 (4'-trifluorOmfethYl-biPheflYl- 2 carbonyl) -amino] -indo1-1-yl1-ace-toxyDethYl) -malonic acid diethyl ester, 2-(2-{2-methyl-4-[ (4'-trifluoromethy1-biphelYl-2- carbonyl) -amino] -benzoimidazo1-1-y1)-aCetoxyflethyl)- 2 phenyl-malonic acid diethyl ester, [2-oxo-3- -trifluoromethyl-biphel2-CarbonYl) 2,3-dihydro-berIZOOXaZOl-6-Yl]-acetiC acid 2,2-bis- ethylcarbafoyl-2-PheflYl-ethYl ester, 2- {3-ethoxycarbonyl-4-1t(4' -trifluoromethyl- biphenyl-2-carbolYl) -amino] -phenyl)-aCetoxyTmethYl) -2- phenyl-Inalonic acid diethyl ester, 2- C3-direthylcarbamoyl-4- 1(4' -trifluoroiethyl- biphenyl-2-CarbOlYl) -amino) -phenyl1-PropiOfllOXYIUthYl) -2- o phenyl-malofiC acid diethyl ester. 4-f -trifluoromethy1-biPheflyl-2-C8IbonYl) -amino] methyll-befzlz~C acid 2, 2-bis-ethylCarbamfOYl-2-Phefl-ethYl ester, -trifluoromethyl-bipheflYl-2-CSaboflYl) 00amnino] -phenyl) -prop ionic acid ethylcarbamfoyl-Phefl-methyl V) ester, o 212 -bis-ethylcarbIl-12-Pheflyl-ethOxcYcarbonYl- methyl) -trifluoromethyl-biPheyl-l2-caxbonYl) -amino] berizoic acid benzyl ester, (2,2-i-tycramy -hnletoyabnl methyl) -trifluoromethYl-biPhefYl-2-CarbonYl) -amino] benzoic a6id, 5- 2 -bis-ethylcarb1DOY1-2-PheflYl-ethOxWcarbonYl- methyl) -trifluoromethYl-biPheflYl-2-CarbonYl) -amino]-- benzoic acid ethyl ester, 2-phenyl-2-(2-f 4 -trjfluoromethyl-biphelyl- 2 carbonyl) -amino] eziidzl1yl-ctxyehl-malonic acid diethyl ester, 3-f -ti urmty-ipey--abnl -amino] rnethyl)-beflzoic acid 3 ,3-bis-ethylc8.rb81fOyl-3-phefylYprOPyl ester, 2-bj 5 -ethyltcarbamoyl-2-phefyl-ethoxycarbOfl methyl) rfuooehy-ihey--cr y) -amino] benzoic acid methyl ester, 2-(3-benzyJlOXycarbofyl-4 -trifluoromethyl- biphenyl-2-CarbOlyl) -amino] -phenyl)-acetoxyfethyl) -2- phenyl-maloflic acid diethyl ester, 0 2-(2-(3-carboxY-4-[ -trifluoromethy1-:biPheflJ2- 0 carbonyl) amino]I -phenyl) -acetoxymethyl) -2 -phenyl-maloflic acid diethyl ester, 2-carbonyl) 3-dihydrO-beflZOOXaZOl- 6 Yl] -acetoxymethy-}- 2 0 V) phenyl-maloflic acid diethyl. ester. Vn carbony)7azabicyc1o[4.2]Octa1(6)24trien3-yl]- o acetoxymethY1).2-Phel-malonic acid diethyl ester, 2-({3-isopropoxyCarbOfl-4-[ -trifluoroITethyl- biphenyl-2-CarbolYl) -amino] -phenyl)-aCetOxYlfethYl) -2- pheny-maJliC acid diethyl ester, 2- (2-(3-methOxycarboflYl- 4 -trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetOX-YrfethY-) -2- phenyl-malOflc acid diethyl ester, 2-2(-iehlabmy--{l(-irl4tiloo inethyl-phel) -pyrrolidine-2-CarbOl]-amino)-phenyl) acetoxymethyl>-2-PhelYl-malolic acid diethyl ester, 2-{3-acetylaliflo-4- -trifluoroxnethy1-biphel1 2-carbOflyl) -amino] -phenyl)-acetOxYflethyl) -2-phenyl-faloflic acid diethyl ester, 2- 3-methoxycarbolylaiflo- 4 'trifluoromnethy1A biphenyl- 2-carbonyl) -amino] -phenyl)I-acetoxymethyl) -2 -phenyl- inalonic acid diethyl ester, 2-2 -4m ty -h a o -l 1 trifluoromfethY1-biPhefl-2-carbonWl) -amino] -phenyl)- acetoxymethyl) -2-phenyl-maloflic acid diethyl ester, 2-phenyl-2-(2-{6-[(4'-trifluorOmfethY-biPhenYlS> carbonyl) -amino] -bipheny1-3-y11-aCetOXYmethYl) -malonic acid Cldiethyl ester, 2-(2-{3-foflfyl-4[ -trifluorOmethYl-biphenyl- 2 en carbottyl) -amino] -phenyl) -acetoxymethyl) -2-pbenyl-malofliC acid diethyl ester, 2- (2-(3-dimethylaminfOme1thYl- 4 -trifluoromethyl- V biphenyl-2-CarbOlYl) -amino] -phenyl1-aCetOKYmethYl) -2- 00 phenyl-malolic acid diethyl ester, o trifluoromethYl-biPhelyl 2-carbonyl) -amino] -phenyll acetox-ymethyl) -2-phenyl-mfaloflic acid diethyl ester, 2-(2-(3-iSObutyryl-4-[ (4'1-trifluorOmfethyl-biPhelYl- 2 carbonyl) -amino] -phenyl1-acetOXYmfethYl) -2-phenyl-maloflic acid diethyl ester, and 2-2(-lhdoy2mty-rpl--(' trifluoromfethY1-biPhefyl-l-carbonYl) -amino] -phenyll-acetoxymn ethyl) -2-phelYl-maloflic acid diethyl- ester.- 23. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of 4-t -trifluorOmethY1ThiPhefyl-l-carbonYl) -amino] phenyl) -acetic acid 2 ;2 -bis -ethylcarbamoyl- 2-phenyl- ethyl ester, 2-phenyl-2-(2-[4- -trifluoromethyl-biPhel- 2-carboflyloxy) -phenyl] -acetoxynethyl)hflalOnic acid diethyl ester, 2-(2-{3-methyl-4-[ -trifluoromethy-biPhenflY- 2-carbonyl) -amino] -phenyl)-acetOXYmfethYl) -2-phenyl-mfalonic acid diethyl ester, (N 2- [methyl- -trifluoromethy1-biPhenl- C) 2 -carbonyl) -amino] -phenyl) -acetoxymethyl) -2-phenyl-maloflic M acid diethyl ester, (3 -ethyl 4- trif luoromethyl -biphenl- 2 -CarbOfl)l amino] -phenyl)l-acetic acid 2,2-bis- ethylcarbamOyl-2-PheflYl- ethyl ester, '-trifluoromethyl-biPhelYl-2-CarbOn~Yl) flamino] -phenyl)-acetiC acid 2,2-trifluoro- o ethylcarbamoyl) -9h-fluoren-9-ylTethYl ester, -trifluoroiflthyl-biphenfl2-CarbOflYl) amino] -phenyl)-propiolic acid 2-trifluoro- ethylcarbamoyl) -9h-fluoren-9-ylnethy. ester, -trifluoromethyl-bipheflYl-2-CarbOnYl) -amino] phenyl)-acetic acid 2-phenyl-2-(2,2,2-trifluOro- ethylcarbamoyl)-ethyl'ester, 2-phenyl-2- -trifluoromethYl-biPheflYl-2 carbonyl) 7ramino] -phenyl) acetoxymethyl) -malonic aciLd die thyl ester, 2-phenyl-2- (2-114- -trifluoromethyl-biPhenYl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -malonic acid diisopropyl. ester, -trifluotomethyl-biPhefl>2-c8bonYl) -amino] phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-trifluorO- ethylcarbamoyl) -ethyl ester, 2-phenyl-2-(2-(4- -trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl}-acetOXymfethYl) -malonic acid dimethyl ester, 2-cyclopentyl-2- 1(4' -trifluoromethyl-biphenYl- 2-carbonyl) -amino] -phenyll-acetOxYmethYl) -malonic acid diethiyl ester, 2-carbonyl) -amino] -phenyl)-aCetOXYmflthYl) -malonic acid dicyclohexyl ester, (4-1(4'-tilooety-ihnl -abnl-amino) phenyl) -acetic acid 2, 2-bis-CYClOhBxylCarb8XOY1- 2 -PhenYl> 00 ethyl ester, -trifluorornethYl-biPheflYl-2-cazbonYl) -amino]- o phenyl)-acetic acid 2-phenyl-2, 2-bis-phelYlcarbamhOY1- ethyl ester, -trifluoromethyl-biPheflYk2-carbonYl) -amino] phenyll-acetic acid 2, ,2bis -sopropylcarbaoyl> -PhenYl- ethyl ester, 2-benzyl-2- 1(4' -trifluOrOmfethyl-biPheflYl- 2-carbonyl) -amino] -phenyl}-acetOXymfethYl-malOflic acid diethyl ester, 2- (2-{2-methyl-4- -trifluoromethyl-biPhelI 2-carbonyl) -amino] -phenyl)-acetoxymfethyl-2-Phefl>*alonic acid diethyl ester, 4' -trifluoromethYl-biPhefll2-carboxcylic acid 4-[2- phenyl-2,2-bis-(2,2,2-trifluoro-ethycarbamoyl)- ethoxycarboflylmethYl] -phenyl ester, biphenyl-2-carboxylic acid 4-1 2-phenyl-2, 2-bis- 2-trifluorO-ethY1CarbafloYl) -ethoxycarboflylfethyll phenyl ester, 2-cyclohexyl-2- 4- [(4'-~trifluoromethY1-biPhelYl- 2-carboflyl) -amino] -pheny1}-aCetoxyflethYl) -malonic acid diethyl. ester, [(biphenyl-2-CarbolYl) -amino] -phenyl)-acetic acid (N 2-phenyl-2, 2-bis- (2 ,2,2-'trif luoro-BthYlCarbaloyl) -ethyl C) ester, 2-phenyl-2-(2-(2-trifluoromethyl- 4 4 trifluoroiethyl-biPhefl-2 -carbonyl) -amino I-phenyl) acetoxymethy)-malOfiC acid diethyl ester, -trifluoromethyl-biphenfl-2-carbonYl) -amino] phenyl)-acetic acid 2. 2-bis-methylcarbXl-2-Phel- ethyl ester, o 2-pyridif-2-yl-2(2df4i(4'-trifluorOmethyl- biphenyl-2-carbOlYl) -amino]-~pheny1}-acetO2CymfethY1-fllOfliC acid diethyl ester, 2-pyridin-3-yl- 2 -trifluoromethyl- biphenyl-2-carbOlyl) -amino] -phenyl}-acetOxymfethYl) malonic acid diethyl ester, 4 -trifluoromethy1-biPhefl-2-carbOxWlic acid 4- (2,2- bis -ethylcarbamfoyl- 2 phenyi-ethOXyCarbOflmethYl) -phenyl ester, 2-hnl2(2(-r lormty--(4'-trifluoro- inethyl-bipheflYl- 2-carbonyl) -amino] -phenyl)- acetoxymethyl)-falOflic acid diethyl. ester, -trifluoromethyl-biphel-2-CarbOlYl) -amino) phenyl)- acetic acid 2, 2-bis-butylcarbamnoY1-2-PheflYl-ethYl ester, {3-methyl-4- -trifluoroniethy1-biphel-l 2 carbonyl) -amino] -phenyl) -acetic acid 2, 2-bis-ethylcrbamOyl- 2-phenyl-ethy- ester, -ehlbihnl2-abnl)a o- phenyll -acetoxyniathyl) -2-phenyl-malonic acid diethyl. ester, (4'-methoxy-biphenyl-2-carboflYl)aminO> phenyl) acetoxyxnethY1) -2 PhelYl-malOni~c acid diethyl ester, (4'-trifluoromethY-biPhenfl2.;CarbOlYl'famino]I phenyll-acetic acid 3, 3-bis-ethylcarbamofl-3Phefl-lPrOPYl ester, 0 -trifluorOmthY1-biPhflY2cabonYll-amino>- C phenyll-acetic acid 3-pheny1-3.3-bis-PrOPYcIbainOYl-ProPYI 00 ester, o 2 (bipheny1-2-CarbOl)-amilO]-Pk18fl)l-acetic acid 2,2-bis-ethylcarba'flY12-PheflYl-ethYl ester, carbonyl) amino] phenyl) -acet OxylethYl) -malonic ac id die thyl ester, 4' -trifluoromethy1-biphefylY2-carbOxWlic acid 4- (2,2- big -ethylcarbalOyl- 2 pheny1-ethOXycarbOlmfethYl) -2- chioro-phelyl ester. 2- [isopropyl- (4'-trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl}-acetOXYmlethYl) -2- phenyl-malolic acid diethyl ester, Lcyclohexyl-(4' -trifluoromethY1-biPhel-2- carbonyl) -am-ino] -phenyl-acetOK-ymfethY.) -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-( 4 4 (4 -trifluoromethy1-biPhel12- carbonyl) -amino) -phenyl-acetOXYmflthY-) -malonic acid dipropyl ester, 2-phenyl-2-(2-{ 4 -t (4'-trif1UOrOmethYl-biPhefl'> carbonyl) -amino] -phenyl)-acetOxymethyl) -malonic acid diisobuty- ester, -trifluoromfethy1-bi~PhefylY2CarbonYl})]1lino]- phenyll-acetic acid 2 ,2-bis-isobutycarbaroy1-2-Phel- ethyl ester, -trifluorOmethYl-biPhenY-2-carbonyl) amino] en phenyl)-acetiC acid 2, 2-bis- 3-methylbutyJlcarbamoYl>> phenyl-ethyl ester, Lethyl-(4-ttfluoromthYl-biphenYl- 2 carbonyl) -amino] -phenyl1-aCetOXYflethYl) -2-phenyl-fa1OfliC 00 '4 acid diethyl ester, -chloro-biPhefl-2-carbonYl) -amino] -phenyl)- o acetic acid 2. 2-bis- (ethylarbamOYl2PhenYl-ethYl ester, 4 v-dich1Oro-biPheylY2carbonY1)-amino]- phenyl)-acetiLC acid 2, ,2-bis (ethylc5rbaIUOYlJ2phenyl-ethyl ester, (3-methyl-4- -trifluoromethy-biphefyl-l> carbonyl)-amilO]-phenyll-aCetic acid 2-pheflyl-2, 2-bis- propylcarbaoYl-ethYl ester, 4- -trifluoroImethylbiPhefylY2carbonYl)> amino]-pheriyJ--acetic acid 2, 2-bis- (2-inethoxy- ethylcarbamfOYl) -2-phenyl-8thY1 ester, 2-2(-ty--('tifurmty-ihnl2 carboflyl)-aliflO] pheny-1-aCetO2CYlfethYl) -2-pheny-maloflic acid diethyl ester, {3-isopropyl- 4 -trifluoromelthy1-biphenyl-2- carbonyl)-.lfifl]-phenyJl)-aCetic acid 2. 2-bis- ethylcarbafOYl2-PhenYi-ethYl ester, 2-(2-(3-iSOPrOPY1- 4 4[( 4 -trifluoromelthyl-biphefyl- 2 carbonyl) -amino] -pheny1)-acetox-y1TethYl) -2-phenyl-malOfic acid diethyl ester, (3-ethyl-4- -trifluoroffethYl-biPhefyl-l carbony1)-amuiflo]PhenYl)-acetic acid 3,3-bis- ethylcarbafoYlJ -phenyl-propyl ester. C) {3-i-sobutyl-4[(4w trifluoromethY1-biPhenfll 2 carbonyl) -amino) -phenyll-acet ic acid 2, 2-bis- ethylcarbW11Oy1--PheflYl-ethYl ester, V')carbonyl) -amino] -pheny11-aCetOXYmethYI) -2-pheny1-ma.OfliC 00 acid diethyl. ester, o carbonyl) -amino] -pheny1II-aCetox-YmethYl) -2-pheflyl-malOfic acid diethyl. ester, carboflyl) -amino] -pheny1I1-aCetOXYflethYl) -2-phelyl-lOfliC acid diethyl ester, 2- 2-{3dimethy1CarbamolY 4 -trifluorometryl- biphenyl-2-CarbolYl) -amino] -pheny1}-acetOXYflIthYl) 2-phenyl-nalOfliC acid diethyl ester, .(3-dimethylCarbamOYl- 4 -trifluoromfethY1- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2-phenyl- 2, 2-bis-propycarbayflY-ethYl ester, {3-methylcarbafollOY 4 -trifluoromethY1-biPhenYl- 2-carbolyl) -amino] -phenyl)-acetiC acid 2, 2-bis- ethylcarbamfOYl- 2-phenyl-ethyl ester, 3- dimethylcarbamolOl-4- trif luoromethyl biphenyl-2-CarbOfl-amino1-phefl1Tacetic acid 3. 3-bis- ethylcarbalfoyl3-PhenYl'ethYl ester, 2- {3-diethylcarbwaloYl- 4 -trifluoromethyl- biphenyl--2-carbolYl) -amino] -pheny11-acetOXymfethYl) -2- pheny.-a1Oflic acid diethyl ester. {3-benzylcarbamfoyl- 4 -trifluorOmethyl-biPhe1Yl- 2 -carbonyl)-amliol-bpheny1>-acetic acid 2 ,2-bis- C) ethylcarbam~oYl -2 -phenyl -ethyl ester; en (3-dinmethylCarbamhOYl- 4 -trifluoromethYl-biPhenYl- 2 -carbony1)-amlilO]phenY1>-acetic acid 4, 4'-bis- ethylcarbwloYl -4 -phenyl -butyl ester, V')(3-diethylCarbarnoYl- 4 -trifluOrOmfethYl-biPhenYl- 2 -carbonyl) -amino] -phenyl)-aCetic acid 2 ,2-bis- kn ethylcarbafoyl- 2-phenyl-ethYl ester, o 41 ~3-diisopropYlCarbafloyl- 4 -trifluoromnethyl biphenyl-2-OarbOlYl) -amino] -phenyll-aceti-c acid 2, 2-bis- ethylcarbafOYl- 2 -phenyl-ethyl ester, 2- (2-(3-dilethYlCarba1oyl- 4 -trifluorOmfethyl- biphenyl-2-CarbOlYl) -amino] -pheny1}-aCetOxCYf1thYl) -2- phenyl-lalofliC acid diethyl ester, 2-{3-diisopropylcarbamoYl- 4 -trifluorofethyl- biphenyl-2-carbonYl) -amino 3-phenyl) -acetoxyinethyl) -2- phenyl-laloflic acid diethyl ester, (isopropyl-flethYlcarbamoYl) -trifluoro- methy1-biPhefYl-2carbonYl) -amino] -pheny2-)-8CetiC acid 2,2- bis-ethylCarb5IDoyl2PhenYl-ethYl ester, 2 2 3 -(ethyl-methylcarbamoyl)v4-[(4 -trifluoro- methy1-biPhel-2-carbo~nYl) -amino] -phenyl}-aCetOXYmfethYl) 2-pheflyl-ma1OfliC acid diethyl ester, (ethyl-methylCarbafOYl) -trifluOromethyl- biphenyl-2-carbOlYl) -amino] -phenyll-acetic acid 2, 2-bis- etbylcarbam1OYl- 2 -phenyl-ethyl ester, (ethyl-methylcarbamoYl) -trifluorOnlethyl- biphenyl-2-carbOlYl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbam~oyl- 3-phenyl-propyl ester, (N (piperidine--carbolyl) -trifluorflfethyl- (1)biphenyl-2-CarbOlYl) -amino) -phenyl)-aCetiC acid 2 ,2-bi-s- ethylcarbafoYl- 2-phenyl-ethyl ester, (pyrroiidine-1-carbolyl) -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetiC acid 2, 2-bis- ethylcarbalOYl- 2-phenyl-ethy- ester, 00 (methyl-propylcarbamoyl) -trifluoromethyl- 0) biphenyl-2-CarbOlyl) -amino]-pheflyl1-aCetiC acid 2 ,2-bis- o ethylcarbaxnoyl-2-PheflYl-ethYl ester, (methyl-propylCarbamfOYl) -trifluoromethYl- biphenyl-2-carbOlYl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbamoyl- 3-phenyl- ethyl ester, (dixnethylcrbafoyl) -trifluoromethY2l- biphenyl-2-CarbolYl) -amino] -phenyl)-acetiC acid 2-ethyl- carbamoyl-2-phefl-thYl ester, 2-phenyl-2- (2-(3-(pyrrolidifelcarbOl)-4- trifluoroznethYl-bipheflYl-2-CarbonYl) -amino] -phenyl)- acetoxymethyl)-malOlic acid diethyl ester, 2-hnl2(-3(ieidn--abnl--(' trifluoromethYl-biPhel-l2'cdrbOnYl) -amino] -phenyl)- acetoxyrnethyl) -malonic acid diethyl ester, (3-dixnethylcarbamOYl-4- -trifluoromfethyl- biphenyl-2-Carbolyl) -amino] -phenyll-acetic acid 2-phenyl-2- propionylamino-ethyl ester, {3-dimethylcarbafoyl-4- -trifluoromethYl- biphenyl-2-carbOlYl) -amino] -phenyl) -acetic acid 2-phienyl-2- propionylamino-ethyl ester, (3-dirnethylcarbamfOYl-4- -trifluoromethyl- biphenyl-2-carbOflyl)-a1Uiflo]Phefl)l-acetic acid 2-(2,5- 417 aioxo-pyrrolidil-1-Yl) -2-phenyl-ethyl ester, C) ~(3-diniethylcarbamfoyl-4- -trifluoromethY2l- Ven biphenyl-2-CarbOflYl) -amino] -pihenylI}-acetic acid 2- ciethylcarbamOyl-befhlbzl ter. (3-dimethYlcarbamfoYl-4- -trifluoroinethyl- biphenyl-2-CarbOl)-ailo] -phenyll-acetic acid 2- 1 thylcrbyalOlmethyl-eZYl ester hdohoie In {-dimethylcarbalflyl-4- -(-trifluoromethyl- o biphenyl-2-CarbOlYl)-amino] -phenyl)-acetiC acid 2l-2 isoproylamino--acidldiethyl esterhdohoie (-3-dimethylcarbaoyl- 4 -turo-ifuroetyl- biphearbnyl-amibolI-phenylo] -penoy)aetxY) -ehyl-?-lo phnlIolcacid diethyl ester, 2marboyl)-WTmifl]-phenyl)-acetOxYflethYl) -2-phenyl-'malonic acid diethyl ester, ini diethylcarbamohefl4l} -acetoxy methpeyl-mlfi acid daithyl eylety ester, {(3-dimethylcarbwfloyl- 4 -trifluoromethyl- biphenyl-2-carbOrlYl)-ainfo] -phenyl)-acetic acid 2- ctyrlanino-2-PhelYl-ethYl ester, 2( -diethylcararbmyl- 4 (-trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyll -acetoxyinethyl) -2- phenyl-ialoflic acid dirnethyl ester, 2-cyclopentyl-2-(2-(3-dimethY1carbamOYl- 4 418 trifluoromethyl-biPhefl>2-carbonyl) -amino] -phenyl} C) acetoxymethyl)-malOlC acid diethyl ester, M -ylhxl2n2(-imtycabmy--(' ci trifluoromethyl-biphel-2-carbonyl) -amino] 0 5 phenyl}-acetoxymethY)-ma.OliC acid diethyl ester, 2-2(-('clr-ihny--abnl-mn]3 00 dime thylcarbafoYl -pheflyl) -acetorymnethYl) 2-phenyl-nalOflic acid diethyl ester, dimethylcarbam~Oyl-phelYl) -acetoxymethyl) -2 -phenyl-ualofliC acid diethyl ester, 2-2(-('caobpey--abnl-mn]3 dixnethylcarbafOYl-Phefll -acetoxyinethyl) -2 -phenyl-maloliC acid diethyl ester, 2-(2-{3-diznethylcarbam1oy-4(4-methyl> 4 trifluoromethyl-biPhel-2-carbonyl) -amino] -phertyl-)- acetoxyrnethyl)- 2-phenyl-malonic acid diethyl. ester, 2-{3-dirnethylcarbamnOYl-4- [(5-methyl-4' trifluoromethyl-biphefl2-CarbOnYl) -amino] -phenyll- acetoxymethyl) -2-phenyl-maloliC acid diethyl ester', C 3-dimethylcarbamfOyl- 4 -trifluoronmethy1- biphenyl-2-carbOlYl) -amino] -phenyl)-abetiC acid 2- methanesulfolylafilO-2 -phenyl-ethyl ester, 3- (2-1 3-dimethylearbwflOYl-4- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyll-aCetoxy) -2-phenyl- propionic acid ethyl ester, (3 -dimethylcarbafoyl-4- -trifluoroinethyl- biphenyl-2 -carbolyl) -amino] -phenyl) -acetic acid 2- (methyl- propionyl-wnino) -2-phenyl-ethyl ester, CI 2 -[3-(2-{3-diLmethy1CarbamOYl- 4 (4'-trifluorOlfethYl- (1)bipheny1-2-C8arbOfYl) -amnino] -phenyl)-acetOSY) -propyl] -2- phenyl-maloflic acid diethyl ester. 2-(2-(3-dimethY1Carbamoyl- 4 (5-methoxy-4'- 0 5 trifluorOmethYl-biPhenYl 2-carboflyl) -amino] -phenyl) acetoxyiethYl-2-PhenYl-malonic acid diethyl ester. 2-(2-{4-[5-chloro-4' -trifluoroznethy1-biphenYl- 2 0' carbonyl) -amino] 3dimethylcarbamlY-Phenfl)l o acetoxynethyl)2-PhenYl-malonic acid diethyl ester. 2 -(2-{3-~di-fethy1carbmoy1-4( 6 -methyl- 4 triiluoronethYl-biPhenYl 2-carbonyl) -amino] -phenyll acetoxymethyl)- 2-phenyl-maloflic acid diethyl ester, 2- 2-t3dimethyCarbamlY- 4 -trif2-uoromethyl- biphenyl-2-carbOlyl) -amino] -pheny1II-aCetOXYmethY))-2- phenyl-maloflic acid di-2.2,2-trif1UOrOethy1 ester, 2- 2-{3dianethY1Carbamoy1-4-[(2' -fluoro-4 trifluoromethYlmbiPhefylY2carbonYl) -amino] -phenyl 1- acetoxymethYJl)2-Phelmalolic acid diethyl ester, 2- 2-{5dimethy1CarbamolOY-2-flUOrO- 4 trifluoromethyl-biPhenyl 2-carbonly) -amino] -phenyl 1- acetoxytfethYl)2-PhelYl-malonic acid diethyl ester, 2 -(2-{3-bromo-5-dimetby1carbamfoyl- 4 4 trifluoromflthYl-biPhenY1-2-carbonYl) -amino] -phenyl)- acetoxymethYl)2-PhenYl-malonic acid diethyl ester, 2 -(2-{3-ch1oro-5-dimlethylcarbamoy- 4 t 4 trifluoromthY2I-biPheflYl- 2-carbonyl) -amino] -phenyl acetoxyrnethyl) -2-phenyl-malolic acid diethyl ester, z-(2-{3-dimethycrbaoy1-4-(3'-fluoro- 4 trifluoromethY1-biPhefylY2carbonYl) -amino] -phenyll- 420 acetox-ymethy)-2-Phenfl-falonic acid diethyl ester, en biphenyl-2-CarbOlYl) -amino] -3-dimethylcarbamoy1-PhenYl}- acetoxymethY1)-2-pheflmalonic acid diethyl ester, 2-(2-{3-dimnethy1CarbafflY4i( 4 '-trifluorOmetby1- V biphenyl-2-carbOlYl) -amino] -phenyI}-aCetOXYf1thYl) -2- 00 (5-nitro-PYridifl-2-Y1)-malon~c. acid diethyl ester, o -trifluoromethy1-biPhefylY2carbonYl) -amino] -pbhenyl)- acetoxymethyl)-maloliC acid diethyl ester, 2- (2-(3-din18thy1CrbamlOYl- 4 -trifluoromfethYl- biphenyl-2-CrbOlYl) -amino) -pheny1)-actoxyflethYl) -2- pyridin-2-y-falOliC acid diethyl ester, 2- 2 3 -chloro-5-diflethYlcrbamoy- 2 fluoro- 4 trifluoromethY1-biPhefl-2-carbonYl) -amino] -pheflyl)- acetoxymethy1)-2-Phel-malolic acid diethyl. ester.- trifluoromethYl-biPhen1Y1-2-carbonYl) -amino] -phenyl)- acetoxymethyl) -2-phenyl-malOnliC acid diethyl ester. 2- 2-{3dimnethylcarbam1foYl- 4 1(4' -trifluorOmethyl- biphenyl-2-Carbolyl) -amino] -phenyl) -acetoxymethyl) -2-o- tolyl-malcrnic acid diethyl ester, 2- (2-{3-dimethylcarbafoYl- 4 U-tritluorcnnethyl- bipheny1-2-Carboli)-amino) -pheny1}-acetOXYmethYl) -2-rn- tolyl-malofliC acid diethyl ester, 2- (2-{3-dirnethy1carbamoyl- 4 -trifluorOmfethyl- biphenyl-2-carbolyl) -amino] -phenyl) -acetoxymethyl) -2-p- tolyl-malolic acid diethyl ester, 2- (2-chioro-phelyl) (2-{3-dimethycarbamfOYl- 4 -trifluoromethYJ-biPheflY12-caboYl) -amino) -phenyl) acetoxymethy)-malOfiC acid diethyl ester, -trifluoromethy1-biPhel2-CarbonYl) -amino] -phenyl)- o acetoxymethyl)-falofliC acid diethyl ester, bi trfl-2ucrbmethY1ThiihnfY12-Cnblfl-l) amino] -pheny- 0 ac~petoymeth1)-aJlnic acid d iethyl ester, o (2-{3-dimethylcabaflOYl- 4 -trifluorofethyl- biphenyl-2-CarbOlyl) -amino] -phenyl}-acetOx-YlfethYl) -2- ph-eyl-succiflicloni acid diethyl ester, 152- (2-(3-dimnethyCarbal-4- -trifluorometbyl- biphenyl carbonyl) -amino I-phenyl I- acetoxymethyl) (23.methoxy-phenfl)-malofliC acid diethyl ester, 2- 2(3-di-methy1CarbThOY1- 4 -trif2-uorOflethiyl- biphenyl-2-carbOlYl) -amino] -phenyll-acetoxyfethyl) -2-(4 acid diethyl ester, 2- (2-{3(4-dmtYCbafiil- F('-trifluoromethyl-bihnl2 biphe'nyl--amiboll -aimino henarayl-eylhl)-- 4 etoxymeh--pheyl)-malonic acid diethyl ester, -amino] -3dimethylcarbafolY-Phefyl)l acetoxyrnethyl) -2-phenyl-Ifalofic acid diethyl ester, 2- (2-{3-dimethyCarbamoflO-4-[ (6-fluoro-4' trifluoromethY)l-biPhenflY2-carbonYl) -amino) -phenyl)- acetoxymethylh2-PhenYl-malonic acid diethyl ester, (N 2-[2-(2-{3-dimethycarbamToy1-4-L(5-methyl- 4' -trifluoromethyl-biphelyl-2-CarbOlYl) -amino] -phenyl)I-' acetoxyethyl) -2-phenyl-malolic acid diethyl ester, 2'-(2-(3-dimethy1carbamol-4-[(5-ethoCy- 4 0 5 trifluoronlethyl-bipheflYl-2CarbOflYl) -amino] -phenyll acetoxyrnethyl)-2-phelYl-malOfliC acid diethyl ester, 00 .4 2-(2-{3-dimnethylcarbalY-4-[E(5-isopropoxy- 4 -trifluoromethy1-biphenfl-2-CarbOlYl) -amino] -phenyll- o acetoxymethy1)-2-Phenfl-ialOniC acid diethyl ester, 2-carbonyl) -amino] -3-dimethylcarbaTOY1-Phefl-aCetoxy) ethyl-2-phel-IalOfliC acid di~thyl ester, 2-(2-{3-dinmethylcarbaoy1-4-(6-methOxt 4 trifluoromethy-biphel- 2 -carbonyl) -amino I-phenyl) acetoxyndthyl)-2-PhelYl-falOflic acid diethyl ester, 2-(2-{3-dimethy1carbamol-4-[(3-methy- 4 trifluoromethy1-biphenY1-2-CarbonYl) -amino] -phenyl)- acetosymethy)-2-PhelflJOniC acid diethyl ester, 2-2[-24 i-rfuooehlbnol io-3- dirnethylcarbalnOyl-Phefl]1-acetoxymethyl) -2 -phenyl-nalonic acid diethyl ester, 2-2(-iehlabmy--('mty-ihnl2 carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl-uialonic acid diethyl ester, 2-{2-I23-direthycarbamoylo-4-(2-thyl4 trifluorohethyl-belZOYlamilo) -phenyl] -acetoxymethy.) -2- phenyl-nialonic acid diethyl ester, 2-(2-{3-dimethycarbalY-4-[ (4'-ethyl-bipheflyl-2- carbonyl) -amino]I -phenyl)-acetoxyfethyl) -2-phenyl-malonic CIacid diethyl ester, 2- (2-(3-dizfethYlcarbaxnOYl- 4 -isoproperyl- en biphenyl-2-CarbolYl) -amino] -pheny3-1-aCetOXYf1thYl) -2- phenyl-faloflic acid diethyl ester, biphenyl-2-Carbolo) -n]pheny1-aCtOXYmethYl) -2-n phelmalo flic acid diethyl ester, [3ehdimethmYlc-ba4-[ 4' -trfiflroifthlety o biphenyl- 2-carbonylo')ai -phenyl -acetic c2ethyley-- in tloni delester, 413-dixnethy1CarbahOYl- 4 -trifluorOmethyl- 2-carbOfl) -amino -phenyl)l-acetic acid 2-eyl- phyl-butylyl ster, (3-dimethylcarbafOyl- 4 -triflWorOmethY- biphenyl-2-CarbOflYl) -amino] -phenyll-acetic acid 1-peny- cylproylnethYl ester, 20(3-dimethylcarblfOyl- 4 -trifluorcnfethyl> biphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2,2eny- dipenyethyl ester, (3-dimethy1CarbamoYlN 4 -trifluoromethYl' biphenyl- 2- carbolyl) -amino] -phenyl)l-acetic acid -henry- cyciopertxymethyl2-hnlpoy ester, {3-dimethyiearbamoyi- 4 -trifiuorofethyl. biphenyi-2-carboli) -amino]I -phenyl)-acetic acid 3-hydroxy- 2 -hyroxymnethvl- 2-phenyl-proPyl ester, 2- (2-{3-dimelthyicarbamfOYl- 4 -trifluoromethyl- biphenyl-2-CarbolYl) -amino] -pheny1)-8CetOXYmflthYl) -2- thiophen-2-yl-flOfliC acid diethyl ester, 2-(2-{I3-dimethy1carbamofl- 4 -trifluorofethyl- biphenyl-2-carbOrlYl) -amino] -pheny1}-aCetOXYmethYl) -2- o 5 thiophen-3-y1-malOflC acid diethyl ester, 2-(2-{4-dimethy1CarbamOY1-5 -trif1uorOflethy1- 00 '4 biphenyl-2-CarbOlYl) -amino] -pyridin-2-Y1Y-aCtOxCYIethYl) 2-phenyl-ialOflic acid diethyl ester, o 2-(2-(3-dimethy1Carbamoyl- 4 -trifluorOflethyl- bi-phenyl-2-carbOlYl) -amino) -pheny11-acetOX-YmethYl) (3- rnethyl-thiopherl-2-YI) -mnalonic acid diethyl ester, 2- (2 dirnethylcarbafOyl trif iuoroniethyl~- biphenyl-2-CrbolYl) -amino] -pheny1)-acetOX-YflethYl) methyl-thiophefl2Y-) -malonic acid diethyl ester. 2- (2-(3-dinethylcarbamfl-4-L (4 -trifluorometh-yl- biphenyl-2-carbOlYl) -amino] -pheny1)-ac8tOX-YflthYl) -2- thiazol-2-y-lalOflic acid diethyl ester, 2-2(-toy4[4-rfurmty-ihnl2 carbonyl) -amino) -phenyl}-azcetOxymethYl) -2-phenyl-mfaloflic acid diethyl ester, (3-hydroxy-4- -trifluoromethy1-biPhelYl- 2 carbonyl) -amino] -phenyl)'-acetiC acid 2, 2-bis- ethylcarbanoyl- 2-phenyl-ethyl ester, {3-methoxy-4- -trifluoromethy1-biphelYl- 2 carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbafOyl- 2-phenyl-ethyl ester, 2- (2-{3-methoxy-4- -trifluoromethY1-biPhflYl- 2 carbonyl) -amino] -phenyl)-acetoxYlfethYl) -2-phenyl-malOflic acid diethyl ester, 3-methoxy-4- -trifluoromethY1-biPhenfl-l> carbonyl) -amino] -phenyl-acetic acid 2-phenyl-2 ,2-bis- propylcarbafoyl-ethYl ester, (3-methoxy-4- -trifluoromethY1-bi~PhnflY carbofl)-amifl]Phefll-acetic acid 3, 3-bis-ethy1CarbamflY3-PhelYl-ProPYl ester., 00 '4 (3-ethoxy-4- -trifluoromethiy1-biPheflYl- 2 0' carbonyl)-amil]-phenyll-acetic acid 2 ,2-bis- o ethylcarbamOy1-2-Phefl-lthYl ester, {3-ethoxy-4- ((4'-~trifl-uoromethyl-biphenll 2 carbonyl) -amino] -phenyll-acetic acid 3 ,3-bis- etLhylcarbalfOYl- 3 -phenyl-propyl ester, 2- 3-isopropOsy- 4 -tritluoromethyl-biphell 2-carbonyl) -amino] -pheny1}-aCtOXYrflthY-) -2-phenyl-falOflic acid diethyl. ester, {3-isopropoxy-4- -trifluoromethY-biPhelYl-2- carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbafol12-PheflYl-BthYl ester, {3-isopropoxy-4- -trifluoromethY1-biPhel-2- carbony))-amino] -phenyll-acetic acid 3, 3-bis- ethyloarbafoyl- 3-phenyl-propy- ester, {3-pr opcxy- 4 -trifluorOrfethY1-biPheflYl- 2 carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbamoyl- 2 -phenyl-ethyl ester, {3-benzylOXy- 4 -tritluoromethyl-bipherl> 2 carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbamfoyl- 2-phenyl-ethyl ester, 2-(2-{3-beflZylOXY-4-1(4' -trifJ.uoronethy1-biPhefl-2- carbonyl) -amino] -pheny1)-acetoxymfethYl) -2-phenyl-malonic CI acid diethyl ester, C) 2-(2-t3--hydrOxy-4-[ (4'-trif1uorOmethYl-biPheny-12 carbonyl) -amino] -phenyl}-acetOXyfethyl) -2-phenyl-TalOfliC acid diethyl ester, 0 2-(2-[3-methOxy-4-[ (4'-tritfluoromethy1-biPhenfl> 2 carbonyloxy) -phenyl] -acetoxymethy)-2-PheflYl-falOnic acid 00 diethyl ester, f3-dinethy-afiflO-4:-[(4' -triiluoroflethy1-biphefyl 2 ocarbony-) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbafoyl- 2-phenyl-ethy- ester, f3-piperidin-1-yl- 4 -trifluoromethY1-biphel-l 2 carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbaloyl- 2-phenyi--ethyl ester, {3-pyrrolidil-J--Yl- 4 -trifluoromethy1ThiphenflYJ 2-carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbamoyl- 2 -phenyl-ethy- ester, 2-pheny1-2-(2-{3-piperidif-lYl- 4 trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyll acetoxyxnethyl)-malOflic acid diethyl ester, 2-pheny1-2-(2-(3-pyrrolidif-1y14-[( 4 trifluoromethyl--biPhefyl>2carbonYl) -amino] -phenyl 1- acetoxymethyl)-malOlic acid diethyl ester, 2- (2-{3-dimethylaliflO-4- -trifluoromethyl- biphenyl-2-carbOlyl) -amino] -phenyl}-acetOxymethyl) -2- phenyl-malOflic acid diethyl ester,. (2-{3-morphOlif-4-Yl- 4 4 (4'-trifluoromethyl- biphenyl- 2-carbonyl) -amino] -pheny1)-acetOS-YmfethYl) -2- phenyl-malolic acid diethyl ester, 2- (2-(3-diethylafiflo-4- -trifluoromethyl- (N biphenyl-2-carbonYl) -amino] -phenyl}-aCetoxymethYl) -2- C) phenyl-faloflC acid diethyl ester, carbonyl) -amino] -phenyll-aCetoxy) -ethyl] -2-phenyl-malolic o 5 acid diethyl. ester, 2-phenyJ.-2-(2-{3-[ (4'-trifluoromethYl-biphel-l2- 00 carbonyl) -amino I -phenyl) -aCetOXYmflthY).) -rnalonic acid diethyl V) ester, carbonyl) -amino] -phenyll-acetoxy) -ethyl] -malonic acid diethyl ester, f3- -trifluoromethyl-biPliefYl-2carbOnYl) -amino] phenyl)-acetic acid 3 ,3-bis-ethylCarbamfl-3-PheflYl- propyl ester, -trifluoromethYl-biPheflYl-2-carbonYl) -amino] phenyl}-aCetiC acid 2 -bis- ethylcarbWUoyl-2 -phenl -ethyl ester, -trifluoromethyl-biPhefl-2-CarbonYl) -amino] phenyl)-acetiC acid 3-phenyl-3, 3-bis- propylcarbamoyl- propyl ester, 2-2(-4mty--('trfurmty-ihnl2 carbonyl) -aminb]-pheflYl)acetoxy-ethY1-2-PhenYl.malonic acid diethyl ester, 2- (2-{2-methyl-5- -trifluoromethyl-biphefl>2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-maloflic acid diethyl ester, -trifluoromethyl-biphenYl2-carbonYl) -amino] phenyll-acetic acid 3, 3-bis-isopropylcarbamfoyl-3- phenyl-propyl ester, {2-xnethyJ--3-[1(4 '-trifluororethY1-biPhenfl-l> carbonyl) -amino] -phenyl)-acetiC acid 3,3-bis- en ethylcarbamoyl- 3-phenyl-propyl ester, {2-xnethyl-3- '-trifluoromethyl-biPheflYl-2 carbonyl)-aninO]-PherlYl)-acetiC acid 4,4-bis- ethylcarbanoyl- 4-phenyl-butyl ester, 00 '4 {2-methyl-3- '-trifluoromethyl-biPheflYl-2- 0' carbonyl)-anfo]-PhefyllacetiC acid 3-phenyl-3 ,3-bis- o propylcarbamoyl-propyl ester, {2-methoxy-3- 1(4' -trifluoromethyl-biphelYl- 2 carbonyl)-arilO]-phenyl)-acetic acid 3, 3-bis- ethylcarbamoyl-3 -phenyl-propyl ester, 2-12- {2-methoxy- -trifluoromethYl-biPhel- 2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl- malonic acid diethyl ester, {2-ethoxy-3-[I(4'-trifluoromethyl-biphelYl- 2 carbonyl) -amino) -phenyl}-acetic acid 3, 3-bis- ethylcarbamoyl- 3-phenyl-propyl ester, 2-12- (2-{2-ethoxy-3- -trifluoromethYl-biPhefl-2 20 carbonyl) -amiLno] -phenyl)-acetoxy) -ethyl] -2-pheYl-aIliC acid diethyl ester, 2-42-(2-{2-isopropoxy-3-[ (4'-trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetoxy) -ethyl] -2- phenyl-naloflic acid diethyl. ester, 2- (2-{2-methoxycarbOnyl-3-[ -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetoxy) -ethyl] -2- phenyl-malOflic acid diethyl ester, 2-2(-2ehx--ehl--('tilooehl biphenyl-2-carbolyl) -amino] -phenyl)-acetoxy) -ethyl) -2- 429 (N phenyl-maloflic acid diethyl ester, C)4- -trif luoronmethYltbiPhefylY2-carbonYI) -arnino] benzoic acid 2-19- (2 ,2,2-trifluOro-8thYlCarbaoyl) -9h- fluorefl-9-yl]-ethYl ester, -trifluoromethyl-biPheflYl-2-CarbonYl) -amino] benzoic acid 2- [9h-fluorefl-9-Yl] -ethyl ester, 00 n-biphenyl-2-Yl-ter8Pbthalamic acid (2,2,2- V)trifluoro-ethYiCarbamOYl) -9h-flUOrefl-9-Yl] -ethyl ester, o 4-f -trifluoromethyl-biPhenfl2-carbonYl) -aniLno] benzoic acid (biphenyl-2-CarbOlYl) -amino) -ethyl ester, -trifluoromethyl-biPheflyl-2-carbonYl) -antino] benzoic acid 2- (2-biphenyl-2-Yl-acet~lamflo)-ethyl ester, 4-C -trifluoromethYl-biPhenYl-2-carbonYl) -amino] benzoic acid 3 -naphthalefl-1-yl-3-i2,2, 2 -trifluoro- ethylcarbalnOyl)-PrOPYl ester, 4-f -trifluoromethYl-biPheflYl-2-carbonYl) -amino] benzoic acid 3- 2,2, 2-triflUOrO-ethYlcarbamOYl) naphthalen-1-Yl] -propyl ester, 4- -trifluoromethYl-biPhefyl-l-carbonYl)-amano] benzoic acid 3 ,3-dipheflyl-3-(2,2, 2-trifluoro- ethylcarbafoyl) -propyl ester, 4- -trifluoromethyl-tiPhefl-2-carbonYl) -amino] benzoic acid S-biphenyl-2-yl-3-(2,2,2-trifluoro- ethylcarbamOYl) -propyl ester, 4- -trifluoromethyl-biPheyl-2-carbonYl) -amino 1- benzoic acid 3-phenyl-3- 2,2-trifluoro- ethylcarbamfOYl) -propyl ester, 4-1(4' -trifluoromethyl-biPhenfl-l>CarbonYl) -amino] benzoic acid 2-18-(2,2,2-triflUOro- 430 (N ethylcarbamoyl) -naphthalefl-1-Yl] -ethyl ester, 4- -trifluoromethy1-bipheflJ2-carbonYI) -amino] en benzoic acid 3- 6-dich.oro-Phefl)-3- 2triflUOrO-ethylcarbamoYl) -propyl ester, 4- -trifluoromethyl-biPhefylY1>cabonYl) -amino] V')benzoic acid 3-2clr-hnl--222tiloo ethylczarbaffOYlh-PrOPYl ester, 2 -phenyl- 2 -(2-4[(4rtrifluoromethyl-biphenyl- 2 o carbonyl) -amino] -benzoyloxYl-Bthyl) -malonic acid diethyl ester, 2-(2-{3-methYl-4-[ (4'-trifluorOmethyl-biPhe8fYl- 2 carbonyl) -amino] -benzoyloxy)-BthYl) -2-phenyl-malOfliC acid diethyl ester, 2-(2-{2-chloro-4-[ (4'-trifluo.rOmethyl-biPheflYl- 2 carbonyl) -amino] -benzoyloxyl-ethyl) -2-phenyl-maloflic acid diethyl ester, 2-phenyl-2-{ 2 -trifluoromethYlbiPhenYl'>- carbonyloxy) -benzoyloxY] -ethyll-malOflic acid diethyl ester, 4- -trifluOrOmethyl-biPhefl>2-carbonYl) -amino] benzoic acid 3,3-bis-ethylCarbamfl-3-PheflYl-ProPYl ester, 4. -trifluoromethyl-biPhefylY1>carboxWlic acid 4- (3,3- bis-ethy2lcrbflOYl3-PhenY1proPoxycarbony) -2-chioro- phenyl ester, 4 F-trifluoromethYl-biPhefl-2-carboxcylic acid 4- (3,3- bis -ethylcarbanOyl -3 -phenyl-proPOXYcarbOlYl) -phenyl ester, 4' -trifluorOmethy1-biPhenY-2-caxboxylic acid 33- bis-ethylcarbamOYl 3PhenY1-ProPoxWcarbonyl) 6-dichioro- phenyl ester, 2- (2-(3-ethoxycarbOfl-l 4 1(4' -trifluorornethyl- bipheflyl-2-CarbOlYl) -amino] -phenyl-aCetOX-YmlethYl) -2- phenyl-malolic acid diethyl ester, 2- (3-{3-dimflthy1CarbamfOYl- 4 '-trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyl}-prOPiOfllOxYmethYl) -2- o ~5 phenyl-malOfliC acid diethyl ester, 2-114- -trifluorOmethYl-biPhnfly2carbonYl) 00 amino] -phenyl) -propionic acid ethylcarbafl-Phefll 0 methyl ester, o 2 2 -bis-ethycarbamoyl2-PhenYl-ethoxycarbonyl- methyl) -trifluoromethYl-biPhefyll2-carbonYl) amino]-benzOiC acid benzyl ester, 2 -bis-ethylcarbamOYl-2-pheflYiethoxWcarbonYl- methyl) -trifluoromfethYLtbiPhenY1>2carbo~nYl) amino] -benzoic acid, 5- (2,2 -bis-ethylcarbamfOyl- 2 pheny1-8thOXYC8arbOfl- methyl) [(4'-tilooety-ihnl -abnl- aminol-benzOic acid ethyl ester, (2,2-i-tyoramy -hnletoyabnl methyl) [(4'-tilooehlbphnl2croy) amino]-beflzOic acid methyl ester, 2- -benzylOXyCarbOnYJl-4- -trif luoromethyl biphenyl-2-carbOflyl)amino] -pheny1}-aCtoxyfl1thYl1 -2- phenyl-malolic acid diethyl ester, 2-(2-(3-carboxy-4-[ -trifluoromethyl-bipheny- 2 carbonyl) -amino] -phenyl}-aCetoxymfethYl) -2-phenyl-mfalOflic acid diethyl ester, 2- 2-{3isoprOpoxycarbOfl> 4 -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -pheny1}-aCetoxyrfethYl) -2- phenyl-malolic acid diethyl ester, (N 2- (2-(3-methoxyCaibOfl> 4 -trifluor'omethY2- biphenyl-2-CarbolYl) -amino] -pheny}-aLCetOX-YmethYl) -2- phenyl-nalofliC acid diethyl ester, 2- (2-(3-acetylaliflO- 4 -[(4'-~trifluorOmflthYl.-biPheflYl- o ~5 2-carbonyl) -amino] -pheny1)-acetOXYmfethYl) -2-phenyl-lalOfliC acid diethyl ester, 00 1- 2- (2-{3-methOXyCarbOflmilO- 4 -trif-luoromethyl- 0 ~biphenyl-2-CarbOlYl) -amino] -pheny1}-aCetOX-YmfethYl) -2- o phenyl-malOliC acid diethyl ester, 2 -(2-{3-(4-methy-thiazo2'ylP 4 4 trifluoromethyl-biPhel-2-carbonyl) -amino] -phenyll acetoxymethYl)2-PhelYl-malonic acid diethyl ester, 2-phenyl-2-(2-( 6 4 -trifluorornethY1-biPhefl- 2 carbonyl) -amino] -bipheny1-3-y1}-8CetoxWImethYl) -ialonic acid diethyl ester, 2-2f-oml4[4-tifurmty-ihnl2 carbonyl) -amino] -pheny1)-actOXYmfethYl) -2-phenyl-latOflic acid diethyl ester, 2- 2{3-dimethy8minoflethYl- 4 -trifluoromfethyl- biLphenyl-2-carbonYl) -amino] -pheny1I1-3-8.CetoxymfethYl) -2- phenyl-nalOfliC acid diethyl ester, 2 -(2-{3-rnethoxy-methY1Carbamoyl) triflUOrOmethYl-biPhefl-2-carbonyl) -amino] -phenyi-)-3- acetoxmethYl)-2-PhnYl-malonic acid diethyl ester, 2-{3-i-sobutyryl-4- -trifluoromethY1-biphienyl- 2-carbonyl) -amino] -pheny1}-3-aCtoxymfethYl) -2-phenyl- malonic acid diethyl ester, and 2- 1hydroxy-2-fethy1-PoPYl) trifluoromethy1-bipheny-2-carbonyl) -amnino] -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 claim 51, which is selected from the group consisting of -trifluoromethYl-bPhenYl 2carbonYl) 1 wino] 00phenyll-acetic acid 2, 2-bis-ethylCarbamoYl) -2-pheflyl- VC) ethyl ester, o 2 -phenyl-2 -2[4[(4U-trifluoromethyl-biphenyl- 2 carbonyloxy) -phenyl] -acetosymethyl) -malonic acid diethyl ester, 2- (2-{3-methyl-4- -trifluoromethYi-biPhenyl- 2 carbonyl) -amino] -phenyl)-acetOX-YmethYl) -2-phelyl-lJoflic acid diethyl ester, 2- [methyl- [(4'-.trifluoromethYlbiPhenyl-2- carbonyl) -amino] -phenylI1-acetOXYflethYl) -2-phelyl-laJlic acid diethyl ester, {3-ethyl-4-[ -trifluoromflthYl-biphenYl> 2 carbony-) -amino] -2-phenyl] -acetic acid 2, 2-bis- ethylcarbalfoylPhefl-ethYl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) amino] -phenyll -acetoxymiethyl) -malonic acid diethyl ester, 2-phenyJl-2- -trifluoronmethYl-biphelYl- 2 carbonyl) -ami-no] -phenyl}-acetOXYmethYl) malonic acid diisopropyl ester, -trifluoromethy1-biPhefl>2-carbonY1)-aminol phenyll-aceti-c acid 2-phefyl-2,2-bis-i 2 2 ,2- trifluorO-ethylcarbamOYl) -ethyl ester, 434 carbonyl) -amino] -pheny1)-acetOXYmethYl) -malonl-c acid Mn dimethy- ester, 2-cyclOpefltyl-2-(2-{ 4 (4'-trifluOrOmethYl- o ~5 biphenyl- 2-carbonyl) -amino)I -phenyl) -acetoxymethy.) -inalonic acid diethyl ester, 00 '4 2-phenyl-2-( 2 4 -t -trifluoromethYl-biPheflYl- 2 0 carbonyl) -amino] -phenyl} -acetoxyrnethyl) -malonic acid 0 dicyclohexyl ester, -trifluoromethyl-biPheflYl-2-carbonYl) -amino] phenyl)-aCetiC acid 2 ,2-bis-cyclohexylcarbamOYl- 2 phenyl ethyl ester, (4'-~trif luoromethyl-biphel12-carbonYl) -amino] phenyl)-acetic acid 2 -phenyl 2 -bis -phenylcarbalOYl- ethyl ester, '-trifluoroxethyl-biPhefylY-2cabonYl) -amnino] phenyl)-acetic acid 2 ,2-bis-isoproPYlCarbamoyl-2-PhelYl- ethyl ester, 2-benzyl-2- -trifluoromethYl-biPhefyl-l> carbonyl) -amino -phenyl) -acetoxyrmethYl) -inalonic. acid diethyl ester, 2- (2-{2-methyl-4-[ -trifluoromethyl-biPheflYl- 2 carbonyl) -amino] -phenyl)-actoxylfethYl) -2-phenyl-malolic acid diethyl ester, 4' -trifluoromnethyl-biPheyl-l2-carboxcylic acid 4- [2- phenyl-2,2-bis-(2,2,2-trifluoro-ethylcarbamoyl)- ethoxycarbonylImethY1] -phenyl ester, biphenyl-2--carboxyliC acid 4- [2-pheflyl-2, 2-bis- 2-trifluoro-ethylCarbamoyl) -ethoxycarbolylmfethyll (N phenyl ester', C) 2-cyclobexyJl-2- -triLfluoroinethYl-biPhel- 2-carbonyl) -amino] I phenyl1-acetOXyfethYl) -malonic acid diethyl ester, [(biphenyl-2-CarbOlYl) -amino]-pheriyl)-aCetiC acid 2-phenyl-2. 2-bis- 2-trifluoro-thYlCarbafOYl) -ethyl 00 ester, 2-phenyl-2-(2-{2-trif1uoromethyl 4 4 o trifluoromethyl-biPhel-2-CarbonYl) -aminol -phenyl)- acetoxymethyl)-malOlic acid diethyl. ester, Wtrif luoromethyl-biPhefl -C8.IbonYl) -amino) phenyl}-acetic acid 2, 2-bis-methylcarbaflOYl-2-Phenfl ethyl ester. 2-pyridin-2-yJl-2-( 2 4 I (4'-trifluorOmfethyl- biphenyJl-2-carbOl) -amino] -pheny1P-acetoxymethYl) -malonic. acid diethyl ester, 2-pyridin-3-yl-2-( 2 4 4 -trifluoromethYl- biphenyl-2-CarbolYl) -amino] -pheny1)-acetOXymethYl) -ralonic acid diethyl ester, 4' -trifluoromethyl-biPheyl-l2-Carbxylic acid 4- 2-bis-ethylCarbamfl) -2pheny1-ethOXYCarbOflmethYl) phenyl ester, 2-phenyl-2- (2-{3-trifluoromethYl-4- trifluoromethyl-biPhel-2-carbonyl) -amino) -phenyl)I- acetoxymethyl)-malOlic acid diethyl ester, -trifluoromethy1-biphefylV2-carbOnYl) -amino] phenyl)-acetic acid 2. 2-bis-butylcarbamoyl-2-PheflethYl ester, {3-methyl-4- -trifluoromethY1-biPhelYl- 2 (Ncarbonyl) -amino]I -phenyll-acetic acid 2, 2 -bis -ethylcarbafoyl 2-phenyl-ethy- ester, phenyll-acetOxymfethyl) -2-phenyl-mfaloflic acid diethyl ester, pheny1}-acetoxymhethYlh-2-phel-falOnic acid diethyl ester. -trifluoromethy1-biPhefl-2-CarbOnYl) -amino] V')phenyll-acetic acid 3 ,3-bis-ethylcarbamflY-3-pheflIPrOPYl o ester, -trifluoromethy1-biPhefl1-2carbonYl) -amino] phenyl) -acetic acid 3 -phenyl- 3,3 -bis-propylcarbafli-propyl ester, (biphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2, 2-bis-ethylcarbaly-2-PheflUethYl ester, 2-phenyl-2- -trifluoromethy1-bipheflI 2 carbonyl) amino -phenyl}-acetOXymfethYl) -malonic acid diethyl ester,, 4' -trifluoromethy1-biphefyl-2carboXYliC acid 4- (2.2-bis-ethylcarbafOyl) -2-pheny1-ethoxyC8-rbolfthYl) 2-chloro-pheflyl ester, 2- [isopropyl- -trifluoromethyl-biPhelyl 2- carbonyl) -amino] -phenyll-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2- (2-{4-[cyclohexyl-(4 -trifluoromethyl-biphelyl- 2 carbonyl) -amino] -phenyl)-acetoxYmethYl) -2-phenyl-malonic acid diethyl ester, 2-phenyl-2-(2-{ 4 (4'-trifluoromethyl-biPhel-2- carbonyl) -amino] -phenyl}-acetOxyl'ethYl) -malonic acid dipropyl ester, carbonyl) -amino] -phenyl) -acetox-ymethyl) -malonic acid M diisobutyl ester, -trifluoromethyl-bipheflYl-2-CarbbflYl) -amino] -phenyll-acetic acid 2, 2-bis-isobutylCarbaloyl-2- phenyl-ethyl ester, -trifluoromethyl-biphenyl-2-CrbOlYl) IC) amino]-phenyl}-acetiC acid 2,2-bis-(3-mfethyl- o butylcarbamoyl) -2-phenyl-ethyl ester, 2-(2-(4-[ethyl-(4'-trifluoromelthy1-biphefyl- 2 carbonyl) -amino] -phenyl}-acetoxynethYl) -2-phenyl-inalonic acid diethyl ester, (4'-chloro-biphelyl-2-carbOlyl)- amino] -phenyfl-acetic acid 2, 2-bis-ethylcarbamoyl-2-phelYl- ethyl ester, (3'4'-dichloro-biphenyl-2-CarbOflyl)- amino] -phenyl}-aczetic acid 2, 2-bis-ethylcarbamoyl-2-phelYl- ethyl ester, {3-methyl-4- -trifluoromethyl-biPhelYl-2- carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2 ,2-bis- propylcarbamoyl-ethyl ester, -trifluoromethyl-:biphenyl-2-CarbolYl) -amino] phenyl)-acetic acid 2, 2-bis- (2-iethoxy-ethylcarbanoyl) -2- phenyl-ethyl ester, 2-(2-{3-ethyl-4-[ -trifluoromethyl-biphelyl-2- carbonyl) -amino] -phenyl) -acetoxymethyl) -2-phenyl-malonic acid diethyl ester, (3-isopropyl-4- 1(4' -trifluoroxnetbyl-bipheflYl-2- carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbamOY>2-PhenYl-ethYl ester, C) 2-(3-isopropyl-4 t -trifluoromethYlbiPhenYl?2 carbonyl) -amino] I phenyl)-aCetOXYflethYl) -2-pheny1-ma1OliC acid diethyl ester, (3-ethyl-4- -trifluoromethyl-biphenYl- 2 carbonyl) -amino] -phenyl)-aCetic acid 3, 3-bis- ethylcarbamfOyl- 3 -phenyl-propyl ester, {3-isobutyl-4- -trifluororethYl-bphnYl>2 ocarboflyl) -amino] -phenyl)-aCetic acid 2. 2-bis- ethyloarball2 -phenyl -ethyl ester, 2- (2-{3-iSObUtYJ-44 (4'-trif luorOmethY1-biPhenY> 2 carbonyl) -amino] -phenyJ)-aCetOXYmflthYl) -2-pheny-fa1OfliC acid diethyl ester, 2-2(-hoo4[4-rfurmty-ihnl2 carbony-) -amino] -phenyl1-acetOXYflIthYl -2phenyl-lalOflic acid diethyl ester, 2 2 3 bromo-4[(4-trifluoromethyl-biphenyl- 2 carbonyl) -amino] -pheny11-aCtOXYflethYl) -2-pheny-malOlic acid diethyl ester, 2 -(2-{3-dimethyCarbalOYl- 4 -trifluorOmethyl- biphenyl-2-Carbolyl) -amino] -pheny1)-acetOX-YflethYl) -2- phenyl-malolic acid diethyl ester, (3-dimethylcdarbafl- 4 1(4 '-trifluorofethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2-phenyl- 2, 2-bis-propYlcarbamhoyleth~Yl ester, (3-metbylcarbaxfl- 4 -trifluorOflethYl-biPhelYl- 2-carbonyl) -amino] -phenyl)-aCetic acid 2 ,2-bis- ethylcarbalOYl- 2 -phenyl-ethyl ester, C 3- diiethylcarbamfoyl [(4'-trifluoromethy-- (Nbiphenyl-2-CarbOlYl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbamOyl- 3-phenyl-propyl ester, 2- 2-{3diethy1CarbaUOY1- 4 -tritluoromethyl- biphenyl-2-CarbOlyl) -amino] -pheny11-aCetOXYmfethYl) -2- phenyl-maloflc acid diethyl ester, V){3-benzyJ-CarbaflOYl- 4 -trifluoromethY1-biPhefl 2 -carbonl1) -a1Tifno]phnyl)Y-acet ic acid 2,2-bis- Vn ethylcarbamOy1-2-phenfl-ethYl ester, o (3-dimethylcarbaloYl- 4 '-trifluoOflethY1- biphenyl-2-CarbOrlYl) -amino] -phenyJ-)-aCetiC acid 4, 4-bis- ethylcarbamoyl-4-PheflYl-bUtYl ester, (3-diethylCarbamOYl-4- -trifluoromethy-biP~hel 2-carbony1)-amilO]-Phefl)l-acetic acid 2,2-bis- ethylcarbamOyl-2-Phefl-ethYl ester, {3-diisoproPY1Carb1flYl- 4 1(4' -trifluoronethy1-biPhel yI-2-carbony)-amfiflo-PhefylY>acetlc acid 2,2-bis- etliylcarbaxnoyl- 2-phenyl-ethyl ester, 2-f 3-diethylcrbaifloyl-4-[(4' -trifluorOnlethyl- biphenyl-2-CarbOlYl) -amino] -pheny11-acetoxymethYl) -2- phenyl-inaloflic acid diethyl. ester, 2- 2-{3diisoproPY1carbamol- 4 -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl-acetOXYmlethYl) -2- phenyl-maloflic acid diethyl ester, {3-(isopropy-methyCarbamOYl) -trifluoromethyl -biphenyl-2-CarbolYl) -amino] -phenyll-acetic acid 2, 2-bis- ethyJlcarbamofl1-2 -phenyl-ethyl ester, 2-(2-{3-(ethy1-methy1carbamoylb4-[( 4 trifluoromethY1-bipheDY1-2-CrbonYl) -amino] -phenyl)- acetoxymethyl) -2-phenyl-nalofliC acid diethyl ester, 440 (N (ethyl-metbylcarbamOYl) -trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyl)-acetic acid 2 ,2-lis- ethylcarbaxnOyl-2-PhenYl- ethyl ester, (ethyl-methylCarbafOYl) -trifluoroinethyl- biphenyl-2-CarbOl) -amino] -phenyll-acetic acid 3, 3-bis- ethylca-rbamoy1-3-Phel-lPropyl ester, (3-(piperidil-CarbOlYl) -trifluorofethyl- VIn biphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2, 2-bis- o ethylcarbanoyl- 2-phenyl-ethyl ester, (3-(pyrrOlidil--CarbolYl) -trifluoromethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetic acid 2, 2-lis- ethylcarbalnOyl-2-Pheflyl-ethYl ester, (methyl-propylCarbalOYl) -trifluoromethyl- biphenyl-2-C8.rbolYl) -amino) -phenyll-acetic acid 2, 2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, (methyl-propylcarbalOYl) -trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetic acid 3,3-his- ethylcarbafoyl phenyl -propyl ester, (3-dimethylCarbafoyl-4- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetic acid 2-ethylcarbaToyl-2-PheflYl-ethYl ester, 2-hnl2(-3proii--abnl--(' trifluoromethYl-biPhefll2'carbonYl) -amino] -phenyl)- acetoxyethyl)-falofliC acid diethyl ester, 2-hnl2(-3pprdi--abnl--(' trifluoromethyl-bipheflyl-2-C'arbonYl) -amino] -phenyl)- acetoxynethyl)-malolic acid diethyl ester, {3-dimethylcarbanoyl-4- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl}-acetiC acid 2-phenyl-2- 0 propionylamino-ethyl ester, S{3 -dimethylcarbwflOYl- 4' (4 '-trifluoromethY1- bipheny1-2-carbOfl)-amiolOphenY1}-acetic acid 2-(2 dioxo-pyrrolidin-1-Yl) -2-phenyl-ethyl ester, (3 -dtmethylcarbwfloyl- 4- 1(4* trifluorOmfethYl- 0 2-ethylcarbanoyl-beflZYl ester, V) (3 -di-nethy1c8~rbamlY> 4 -trif luorOflethYl- o biphenyl- 2-carbonyl) -amino] -pheriylj -acetic acid 2- ethylcarbamoyllmethyl-beflzyl ester, 3-dimethylCarbafOYl- 4 -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetiC 'acid 2- isopropylaino -2 -phenyl -ethyl ester hydrochloride, 2-[2-(2-.{3-diLmethY1CarbamOYl- 4 -E -trifluoromethyl- biphenyl-2-CarborIYl) -amino) -phenyll-acetoxy) -ethyl] -2- phenyl-malolic acid diethyl ester,- 2-(2-{3-dirnethy1CarbamlY-44[( 4 -fluoro-bipheflyl-?- carbonyl) -amino] -phenyl) -acetosyniethyl) -2-phflyl-faloflic acid diethyl ester, 2-2(-('boobpey--abnl-mnj3 dimethylcarbamoYl-Phel)I-acetozymethyl) -2 -phenyl-malolic acid diethyl ester, {3-dimethylcarbamfOYl-4- -trifluoroinethyl- biphenyl-2-CarbOlYl)-amino) -phenyll-acetic acid 2-acethylamiflo-2-PheflYl-ethYl ester, (3-dimethylcarbafOyl- 4 '-trifluoromethYl- biphenyl-2 -carbor'yl) -amino] -phenyl) -acetic acid 2-butyrylalinO-2-pheflYl-ethYl ester, 2-{3-dimethylcarbamfl-4- -trifluoroinethyl- (N biphenyl-2-carbOlYl) -amino) -pheny1)-acetOXYfllthYl) 2-pheny--maliC acid dimetbyl ester, trifluoromethyl-biphelyl 2 -carbonyl) -amino] -phenyll 0 5 acetoxymethyl)-falOfliC acid diethyl ester, trifluoromethyl-biPhel-2-carbonyl) -amino] -phenyl) V')acetoxymethyl)-falOflic acid diethyl ester, diniethylcarbalnoYl-Phel)}-acetoxymethyl) -2 -phenyl-Inaloflic acid diethyl ester, 2- -icetyl-biphenyl-2-CarbOlYl) -amino -3- dimethylcarbamoyl--PhenYl} -acetoxymethyl) -2-phenyl-Inalonic acid diethyl ester, 2-2(-('caobpey--abnl-mn]3 dinethylcarbaloYl-PheflYl) -acetoxyrnethyl) 2-phenyl-mfaloflic acid diethyl ester, 2-(2-{3-dimethylcarbamoy-4-[(4-methyl 4 trifluromethyl-biPhel-2-carbonyl) -amino] -phenyl) acetoxymethyl)-2-Phefl-malonic acid diethyl. ester, 2-f 3-diniethylcarbamoYl-4- [(5-methyl-4' 'trifluromethyl-biphel>2 -carbonyl) -amino! -phenyl) acetoxynethyl)-2-Phelyl-maloflic acid diethyl ester, (3-dirnethylcarbamoyl-4- 1(4' -trifluoromethyl- biphenyl-2-CarbonYl) -amino] -phenylil-acetic acid 2-nlethanesulfoflamfino-2PheflYl-ethYl ester, 2-{3-dimethylcrbamfoyl-4- -trifluoromethyl- biphenyl-2-CarbonY-) -amino] -phenyl)-acetoxy) -2-phenyl- propionic acid ethyl ester, {3-dimethylCarbamfOyl1- 4 -trifluoromflthY1- biphenyl-2 -cabolyl) -amino] I phenyl)}-acetic acid 2- (methyl- M propionyl-amilo) -2-phenyl-ethyl ester, 2-[3-(2-(3-dimethy1CrbamrfOYl-44 (4'-triflurOmfethYl- o ~5 -biphenyl-2-oarbOflYl) -amino] -phenyl)-aCetOXY) -propyl] -2- phenyl-naloflic acid diethyl. ester, 2 -(2-{3-dimethylcarbmoyl4[(5-methoxy 4 0' trifluromethy1bipheflYl-2-carbonYl) -amino] -pheflyl) o acetoxymethy1)-2-PheflYl-malOnic acid diethyl ester, carbonyl) -amino] -3 -dimethylcarbamfOYl-PhelYl)- acetox-ymethyl) -2 -phenyl-malOflc acid diethyl ester, 2 -(2-{3-dimethylcarbmoyl-4-[(6-mfethyl- 4 trifluoromethYl-biPhelyl 2 -carbonyl) -amino] -pheny)- acetoxymethYl)-2-PheflmalOnic acid diethyl ester, 2-(2-(3-dimethylCarbamOYl-4K -trifluoromethyl- -biphenyl-2-carbOflYl) -amino] -phenyl-aCetOSYmfethY.) -2- phenyl-maloflic acid di-2, 2, 2-trifluoroethyl ester, 2- (2-{3-dimethylcarbamOYl- 4 -fluoro-4' trifluoromethyl-biPhefl2-CarbOnYl) -amino] -phenyl}- acetoxymethy1)-2-Phel-lmalOfliC acid diethyl ester, 2- 5-dimethylcarbamOy1-2-fluoro- 4 trifluoromethyl-biphel-2-carbonyl) -amino] -phenyl 1- acetoxymethyl) -2-phenyl-naliC acid diethyl ester, 2-2{-rm--iehlabmy--(' trifluoromethylbiPhenY1>2carbonYl) -amino] -pheriyll- acetoxymethyl) -2-phenyl-Inalonic acid diethyl ester, 2- (2-{3-chloro-5-dIlethYlcarbamfoyl- 4 trifluoromethy1-bipheflyl-2'-carbonyl) -amino] -phenyl)- acetoxymethyl-2-Phefl-malonic acid diethyl ester, C) 2-(2-{3-dimethY1CarbanoYl- 4 -i (3'-fluorO-4'- en trifluoromethyl-biphel-2-carbonyl) -amino] -phenyllI- acetoxymethy1)-2-PhenYl-malonic acid diethyl ester. carbonyl) -amino] -3-disnethy1Carbamfl-PhelYl) 00 1- acetoxymethyl-2-Phefl-malonic acid diethyl ester, 2- 2-{3dimethy1C8.rbamOYl> 4 -trifluorofetbyl- o ~biphenyl-2-carbolYl) -amino] -pheny1}-aCetOXYffethYl) nitro-pyridin-2-Y)l)-malOnic acid diethyl ester, 4- -trifluoromethY1Zbiphel2-carbonYl) -amino) phenyl) -acetoxymethyl) -malonic acid diethyl ester, 2- (2-{3-di*methY1Carbamfoyl- 4 -trif luorOmfethY-yl biphenyl-2-carbonYl) -amino] -pheny1)-aCetOXYmfethYl) -2- pyridin-2-y1-malOliC acid diethyl ester, 2-2(-hoo5dmtylabmy -loo4[(4'- triflnoromethYl-biPhefl-2>cabonYl) -amino] -phenyl)- acetoxymethy1)-2-phelJmalonic acid diethyl ester, 2-2{-rm--imtycraol2fur-- trifJluoromethYl-biPhefl2-carbonYl) -amino] -phenyl)- acetoxymethYlb-2phenyl-malonic acid diethyl ester, 2-C 3-dimethylcarbamloyl- 4 -triflnoromethyl- biphenyl-2-C8.rbolYl) -amino] -pheny1I-a.CetOXYIethYlY 2 -o- tolyl-malonic. acid diethyl ester, 2- (2{3-dimethY2lCarbamoyl- 4 -trifluoromethyl- biphenyl-2-CarbOl-amino]-phenY1)-aCetox-YmflthYl) -2-rn- toly-ifaloflic acid diethyl ester, 2-(2-{3-dimethy1carb8Thoyl- 4 -trifluorometh-yl- 445 (N biphenyl-2-CarbOflYl) -amino] -pheny11-acetOXYmflthYl) -2-p- C) tolyl-malonic acid diethyl ester, -trifluoromethy1-biPhefylY1>CarbonYl) -amino] -phenyl)- o ~5 acetoxyniethyl)-malOlic acid diethyl ester, 2-3clr-hnl--2-3dmtycraol4 00 '4 -trifluoromethY1-biPhefylY12CarbonYl) -amino] -phenyl)- acetoxyniethyJl)-malOnic acid diethyl ester, -trifluoromethy1-bipheflL2-CarbonYl) -amino) -phenyl)- acetox-ymethyl)-malolic acid diethyl ester, 2- (2-(3-dimethylcarbalOyl- 4 t -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetOXYmflthYl) -2- phenyl-succilic acid diethyl ester, 2- (2-{3-dimethylcarbamOYl-4- -trifluorOmfethyl- biphenyl-2-carbonyl) -amino] -pheny1)-8CetOXYmflthYl) (2- methoxy-phenyl)-malOnic acid diethyl ester, 2- (2-{3-dimethylcarbafOYl- 4 -trifluoromethyl- biphenyl-2-carbOlYl) -amino] -pheny1)-8cetOXYmethYl) (3- methoxy-phenYl)-malOflic acid diethyl ester, 2-{3-dimethylCarbafOYl- 4 -trifluoromethyl- biphenyl-2-carbonyl) -amino] -pheny1)-aCetOXYmethYl) (4- methoxy-phenyl)-malolic acid diethyl ester, carbonyl) -amino] 3di-methylcarb1TOY1-PhenYl)}- acetoxymethyl)-2-PhenYl-malonic acid diethyl ester, (6-chloro-4'-trifIUOromfethYl-biPhenYi- 2 carbonyl) -amino) -3-dinmethylca-rbamflY-PhenYl)> acetoxymethyl) -2-phenyl-malolic acid diethyl ester, 446 2-(2-{3-dinmethYJ.Carb1oyl> 4 C (6-fluoro-4'- C) trifluorometbYl-biPhenYl±2-cabofYl) -amino) -pheny- en acetorymethYl)2-Phel-malonic acid diethyl ester, ci 2 2 2 -(3..dimethylcarbamoy1-4-[(5-methyl- 4 0 5 trifluoronethYlmbiphenyl- 2 -carbonyl) -amino] -phenyl- acetoxy) -ethy] 2-PhenYl-malonic acid diethyl ester, 2-(2-{3-dimfethY1Carbamoyl- 4 (5-ethoxy-4'- V) ~trif luoromethYl-biPhenyl- 2 -carbonyl) -amino] -phenyl) o acetoxymethyl)2-phenYl-malonic acid diethyl ester. 2 2 -{3-dimethy1carbamoy1-4-(5-isopropocy- 4 trifluoromethY1l-biPhel-2-carbonyl) -amino] -phenyll acetoxymethY1)-2-phel-lmalonic acid diethyl ester, carbonyl) -amino] -3-dimfethyJ.Carb8IfyloYPhefylY1acetory) ethy1]-2-phel-maloliC acid diethyl ester, 2-{3-dimethylcarbaifl- 4 -(6-inethoxy-4' trifluoromethYlbiPhenyl-2carbonyl) -amino] -phenyll- acetoxymethY1-2-Phen~Yl-malonlc acid diethyl ester, 2- (2-{3-dimethy2-Carbamoyl- 4 I(3-methyl-4 trifluoromethYl-biPheflYl-2-carbonYl) -amino] -phenyll- acetoxymethyl)2-PhenYl-malonic acid diethyl ester, 2 2 4 2 ,4-bis-trif1uoromethYl-benzoYlamino) -3- dimethylcarbafoyl>Phel'-acetoxytnethyl 1-2 -phenyl-malofliC acid diethyl ester, 2 3 -dimethy1carbaoylOY1-(4methYlbiphenyl>> carbonyl) -amino] -phenyl)-acetoxyfethYl) -2-pheny-laIliC acid diethyl ester, 2-(2-[3-dimethy1carbamoyl> 4 -[(2-ethyl-4- trifluoromethylThelzoyJamino) rpheiyi-]-acetoxymethyll -2- 447 pheny1-maOliC acid diethyl ester, 2-(2-(3-dirnethy1Carbamol- 4 4 (4'-ethy1-biPhenfl-r> carbonyl) -amino]-~pheny11-aCetOXYIUethYJl) 2-phenfl-aJOfliC acid diethyl- ester, 2- C2-C3-dimethY1CarbafOYl- 4 -isopropenyl- biphenyl-2-CarbolYl) -amino) .pheny1}-aCetOXYmfethYl) -2- 00 phenyl-malolic acid diethyl ester, 2 2 -{3-dimethyIcarbmoy-4[(4-isopropyl- o biphenyl-2-CarbOflYl) -amino) -pheny1}-aCetOX-YIethYl) -2- phenyl-ma-OfliC acid diethyl ester, [3-dimethylcarbamfOYl- 4 -trifluorofethy- biphenyJ--2-CarbOfloY2)-phenyll -acetoxymethyl- 2 phenyl-malolic acid diethyl ester, 3-dimethylcarbamoYl- 4 -trifluoromfethyl- biLphenyl- 2-CarbOlYl) -amino -phenyl) -acetic acid 2-ethyl- 2-phenyl-butyl ester,- (3-dimethylcarbafOYl- 4 -trifluoromethyl- biphenyl-2-CarbOlYl) -amino) -phenyl)-acetic acid 1-phenyl- cyclopropylinethyl ester, {3-diniethylCarbdmOYi- 4 -trifluorOmethYl- biphenyl-2-carbOlYl) -amino] -phenyll-acetic acid 2,2- diphenyl-ethyl ester, (3-dimethylCarbamfoyl- 4 -trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyl)-acetic acid 1-phenyl- cyclopentylmethyl ester, {3-dimethylcarbamoYl- 4 -trifluoroinethyl- bipheflyl- 2-carbolyl) -amino] -phenyll -acetic acid 3-hydroxy- 2 -hydroxyxnethyl-2-PhenYl-ProPYl ester, 3-dimethylarbafoyl- 4 -trifluoronlethyl' (N biphenyl-2-CarbOlYl) -amino] -phenyll-acetic acid 3-acetoxymethY1-2-PhefllPr)PYl ester, 2-(2-{3-dinethy1CarbaxnOY1-4-[ -trifluorotnethyl- biphenyl-2-carbOlYl) -amino] -pheny11-aCetOXYfl1thYl]-2'- thiophen-2-Y-lalOfliC acid diethyl ester, 2- (2-{3-dinethy1CarbamOY1-4K -trifluoromiethyl- 00 biphenyl-2-CarbOlYl) -amino] -phenyfl-aCtOXYmfethYl] -2- V)thiophel-3-Y-falOfliC acid diethyl ester, o 2- (2-{4-dimethy2.Carbamofl-54( 4 -trifluorontethyl- biphenyl-2-CarbOlYl) -amino] -pyridin-2-y1)-aCetOXYI1IthYlV- 2-phenyl-malolic acid diethyl. ester. 2- (2-3-dimethyCarbamOY1-44[( 4 '-trifluorozuethyl- biphenyl-2-Carbol) -amino] -pheny1)-aCetoxymfethYl] (3- methyl-thiophen-2>Yl) -malonic acid diethyl ester, 2- (2-{3-dimethylcarbafoYl- 4 -trifluorotnethyl- biphenyl-2-CarbOlYl) -amino) -pheny1)-acet-OXYmfethYl) methyl-thiOphefl-2-Yl) -nalonic acid diethyl ester, 2- (2-{3-di'ethylcarbamfOYl- 4 -trifluoromethyl- biphenyl-2-carbolyl) -amnino] -phenyl)-acetox-Yflethyl) -2- thiLazol-2-y-malOfliC acid diethyl ester, 2-2 -toy4[4-rfurmty-ihnl2 carbonyl) Zainino] -pheny1)-actoxymtethYl) -2-pheny--maloflic acid diethyl ester, {3-hydroxy-4- 1(4' -trifluoron'ethY1-biPhefl- 2 carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbaloyl- 2-phenyl-ethyl ester {3-methoxy-4- -trifluoroniethyl-biphelYl- 2 carbonyl) -amino] -phenyl)-aCetic acid 2, 2-bis- ethylcarbamfoyl- 2-phenyIl-ethy1 ester 449 carbonyl) -amino] -phenyl}-acetOxymethyl) -2-pheflyl-malOflic acid diethyl ester, {3-methoxy-4- -trifluoromethyl-biPhefyl-l> carbony)-amfiflO]-PheflTacetic acid 2-phenyl-2 ,2-bis- propylcarbainoyl-ethyl ester, 00 '4 (3-rnethoxy-4- -trifluoromethY1-biPhefl- 2 0carbonyl) -amino] -phenyl)-acetic acid 3, 3-bis- o ethylcarbamfoyl- 3-phenyl-propyl ester, {3-ethoxy-4- -trifluoromethY1-biPhelYl- 2 carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbalnoyl-2-phel-ethyl ester. {3-ethoxy-4- '-trifluoromethyl-biPhefl-l' carbonyl) amino] -phenyl)-acetic acid 3,3-his- ethylcarbamoyl-3-phelYl'-PEOPYl ester, 2-{3-isoprOpoxy-4- -trifluoromethyl-biPhefyl-l> carbonyl) -amino] -phenyl)-acetoXYmfethYl) -2-phenyl-maloflic acid diethyl ester, (3-isopropoxy-4- -trifluoromfethyl-biPhelYl- 2- carbonyl) -amino] -phenyll-acetic acid 2,2-his- ethylcarbamfoyl- 2-phenyl-ethyl ester, (3-isopropOxy-4- -triiluoromethY1-biPhelYl- 2 carbonyl) -amino] -phenyl)-acetic acid 3,3-his- ethylcaraloy-3-phenyl-propyl ester, (3-propoxy-4-1(4' -trifluoronmethYl-biPheflYl-2 carbonyl)-amilO]-phenyll-acetic acid 2,2-his- ethylcarbamoyl- 2-pheflyl-ethyl ester, {3-benzyloxy-4- -trifluoromethY1-biPhel) 2 carbonyl) -amino] -phenyl)-acetic aciLd 2,2-his- etiwlcarbaxnoy1-2-pheny1-ethYl ester, O 2- (2-(3-benzylOXY-4- -trifluorometbY1-biPhenfl-l> carbonyl) -amino) -phenyl1- acetoxymethyl) -2 -phenyl -ialonic acid diethyl ester. carbonyl) -amino] -pheny11-aCtOX-YflethYl) -2-phenyl-faJliC 00 '4 acid diethyl ester, Vfl 2-(2-[3-methoxY-4-(4' -trifluoromethy1-biPhel-l 2 o carbonyloxy) -phenyl) -acetoxyzethy1T2-Pheflmalonic acid diethyl ester, f3-dirnethylanfO- 4 -trif1uoromethyl-biPhenfl 2 carbonyl) -amino1-phefl-aCetiC acid 2, 2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, f3-piperidin-1-Yl- 4 -trifluoromethY1-biPhefl-2 carbonyl) -amino] -phenyl)l-acetic acid 2, 2-bis- ethylcarbalfOyl-2-PhefyllethYl ester, {3-pyrrolidifl-l-yl- 4 -trifluoromethy1-biPhefl 2- carbonyl) -amino] -phenyll-acetic acid 2,2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, 2-pheny1-2(2f3-piperdin1y-4( 4 trifluorOmethY1-biPhefl2-CarbonYl) -amino] -phenyl)- acetoxymethyl)- malonic acid diethyl ester, 2-phenyl-2- (2-f 3-pyrrolidill-1-yl- 4 trifluoromethY1-biPhefl-2-CarbonYl) -amino) -phenyl)- acetoxyrnethyl)- malonic acid diethyl ester. 2- (2-(3-dimethylafiflo-4- -trifluoromethyl- biphenyl-2-CarbOnYl) -amino] -phenyll-aCetoxymfethYl) -2- phenyl-m~aloflic acid diethyl ester. 2-(2-{3-morPholif-4-yl-4- 1(4' -trifluoromethy- 0 ~biphenyl-2-carbOlYl) -amino] -phenyll-acetOxylethyl) -2- phenyl-malonic acid diethyl ester, 2-(2-{3-dithylafiflO-41 (4'-trifluorofethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxyfethYl) -2- phenyl-maloniC acid diethyl ester, 00carbonyl) -amino] -phenyl}-acetoxy) -ethyl] -2-phenyl-nalolc acid diethyl ester, carbonyl) amino]I -phenylJ acetoxymethYl) -malonic acid diethyl ester, 2-hnl2[-2(-('trfurmty-ihnl2 carbonyl) -anino]-phenyl}-acetOxy) -ethyll-malonic acid diethyl ester, -trifluoromethyl-biphelyl-2-CarbOlYl) -amino) phenyl)-acetic acid 3, 3-bis-ethylcarbanOYl-3-PhelYl- propyl. ester, trif luoromethyl -biphenlyl- 2- carbolyl) amino] phenyl}-acetic acid 3-phenyl-3, 3-bis-propylcarbamol- propyl ester, 2- (2-{4-methyl-3- -trifluoromethyl-biphelYl-2- carbonyl) -amino] -phenyll -acetoxy) -ethyl) -2-phenyl-rialonic acid diethyl. ester, 2-2(-2mty--('trfurmty-ihnl2 carbonyl) amino]I phenyl) -acetoxy) ethyl] -2-phenyl -malonic acid diethyl. ester, -trifluoromethyl-biphelyl-2-Carbolyl) -amino] phenyl)-acetic acid 3, 3-bis-isopropylcarbaJLmOYl-3- phenyl-propyl ester, 452 {2-methyl-3- -trifluoromethYl-biPhel- 2 carbonyl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbazuoyl-3 -phenyl-propyl ester, {2-methyl-3- U-trifluorornethyl-biPhefll 2 carbonyl) -amino] -phenyl)-acetiC acid 4, 4-bis- ethylcarbamoyl-4-pheflyl-butYl ester, {2-methyl-3- -trifluoromethyl-biPhnfl-l 2 carbonyl) -amino]-phenyl)-aCetic acid 3-phenyl-3 ,3-bis- propylcarbamoyl-propyl ester, (2-methoxy-3- -trifluoromethyl-bipheflyl- 2 carbonyl)-amxino] -phenyl)-acetiC acid 3, 3-bis- ethylcarbamOyl-3-PheflYl-PrOPYl ester, 2-12- (2-(2-niethoxy-3- -trifluoroinethyl-biphefl 2-carbonyl) -amino] -phenyl)-acetoxy) -ethyl) -2-phenyl- malonic acid diethyl ester; {2-ethoxy-3- -trifluorOmfethyl-bipheflYl- 2 carbonyl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbamoyl- 3-phenyl-propyl ester, 2-2(-2ehx--('trfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxy) -ethyl] -2-phenyl-ma-lonic acid diethyl ester, 2-112- (2-{2-isopropbxy-3- 1(4' -trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyll-acetoxy) -ethyl] -2- phenyl-malolic acid diethyl ester, 2-[2-(2-{2-methOxycarbOflyl-3-1(4'-trifluoromethy.- biphenyl-2-carbolyl) -amino] -phenylj-acetOXy)-ethYl] -2- phenyl-malonic acid diethyl ester, 2-[2-(2-f2-etholy-5-lethyl-3-[( 4 -trifluorometbyl- biphenyl-2-carbOlYl) -amino] -phenyll-acetoxy) -ethyl]-?- phenyl-maloflic acid diethyl ester, 4-1(4' -trifluoromethyl-biPhefl-2-cabOflYl) -amino] benzoic acid 2-I (biphenyl-2-carbOlYl)-afil-ethyl ester, -trifluoromethyl-biphenfl-2-CarbOnYl) -amino] benzoic acid 2- (2-bIphenyl-2-y-aCtYalfO) -ethyl ester, ~~fl 4- -trifluoromethy1-biPhenfl-2-CarbonYl)-amino] 00 benzoic acid 3-naphthalefl-1-Y1-3- (2,2,2- V)trifluoroethylCarbamOYl) -propyl ester, o '-trifluoromethyl-biphel-2-C.rbolYl) -amino] benzoic acid 3-[2-(2,2,2-trifluoro- ethylcarbamoyl) -naphthalen- 1-yl] -propyl ester, 4- -trifluoromethyl-biphefl1-2-CarbolYl)-amino] benzoic acid 3, 3-diphenyl-3-( 2,2, 2-trifluoro- ethylcarbamoyl) -propyl ester, (4 -trifluoromethyl-bipheflYl-2-CarbolYl) -amino] benzoic acid 3-biphenyl-2-y1-3- 2-trifluoro- ethylcarbamoyl) -propyl ester, 4- '-trifluoromethy1-biphelYl- 2-carbonyl) -amino] benzoic acid 3-phenyl-3- 2,2-trifluoro- ethylcarbamoyl)-PropyI ester, 4- -trifluoromethy1-biphefl-2-CarbOnYl) -amino] benzoic acid 2- 2, 2-trifluoro-ethylcarbafliOYl) naphthalen-1-yl] -ethyl ester, 4- [(4'-~trifluoromethyl-biphenyl-2-CarbolYl) -amino] benzoic acid 3-(2,6-dichloro-pheflyl)-3-(2,2.2-triflUOro- ethyJlcarbamoy1)-Propyl ester, 4-1(4' -trifluoromethyl-biphelyl-2-CarbolYl) -amino] benzoic acid 3-(2-ch1oro-pheflyl)--(2,2,2-trifluoro- ethylcarbam~oYl) -propyl ester, 454 carbonyl) -amino] -benzoylosy)-Sthyl) -malonic acid diethyl ester, Ci 2-(2-{3-methyl-4-[ -trifluoromethy1-bipheflYl- 2 carbonyl) -amino] -benzoyloxy) -ethyl) -2-phenyl-maloflic acid diethyl ester, tncarbonyl) -amino] -benzoyloxy}-ethyl) -2-phenyl-maloflic acid o diethyl ester, 2-phenyl-2-{2-[4-( 4 -trifluorOmfethY1-biPheflYl- 2 carbonyloxy) -ben zoyloxy]I -ethyl)l-malOlic acid diethyl ester, 4- -trif luoromethy1-biPhel-2-CarbonYl) -ami-no] benzoic acid 3, 3-bis-ethylcarbamnOyl-3-PheflYl-PrOPYl ester, 4' -trifluoromethy1-biPhel-l2-CarbOxWlic acid 4- (3,3- bis ethylcarbamoyl 3- phenyl propoxycarbonyl) 2- chioro phenyl ester, 4' -trifluoromethyl-biphefylY-carboxylic acid 4- 3 -bis-ethylcarb8Xl-l3-PheflYl-ProxycarbonYl) -phenyl ester, 4' -trifluoromethyl-biPhel)2-Carboxcylic acid 4- (3,3- bis-ethylcarbamOyl-3-PhenYl-PropoxWcarbonYl) 6-dichloro-p henyl ester, 2- (2-{3-ethoxyCarbOflYl-4-[ -trifjluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl}-acetoxymfethYl) -2- phenyl-maloflic: acid diethyl ester, 3-{3-diznethy1carbafolY 4 -trifluoromethyl- biphenyl-2-carbOlYl) -amino] -phenyl}-prOpiOfllOXYmethYl) 2-phenyl-mfalofliC acid diethyl. ester, 4- -trifluoromfethyl-biPheflYl-2-CarbOflYl) 455 (N amiino] -phenyl)}-propionic acid ethylcarbamOYl-PheflI C) methyl ester, (2,2-i-tycramy -hnletoyabnl methyl) -trifluorOrfethY1-biPhefYl-2-carbonYl) axino]-benzoic acid benzyl ester, (2 2 -bis-ethyicarbamfl-2-Phefl-lethoxcacbol- 00methyl) -trifluoromethYl-biPhefl>2-caboflYl) In amino]-beflzOiC acid, o 5- 2 -bis-ethylcarbamoyl-2-PhelethoxcYcarbonYl- methyl) -trifluoromethYl-biPheflYl-2-carbonyl) amino]-benzoic acid ethyl ester, (2,2-i-tycramy -hnletoycLbnl methyl) [(4'-tilooety-ihnl -abnl- amnino]-ber'zoiC acid methyl ester, 2-{3-beflZylOXYCarbOfYl- 4 -trifluorOmethYl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxyifethyl) 2-phenyl-faloflic acid diethyl ester, 2-2{-abx-7('tifurmty-ihnl2 carbony-) -amino] -phenyl)-acetoxymethyl) -2-phenyl-malolic acid diethyl ester, 2- (2-{3-isopropoxycarbonyl-4- -trifluorofethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxymethyl) -2- phenyl-faloflic acid diethyl ester, 2- (2-{3-methoxycarbOfl-l 4 -trifluoromnethyl- biphenyl-2-CarbOlYl) -amino] -phenyl}-acetoxymfethyl) 2- phenyl-fllOfliC acid diethyl ester, 2-(2-{3-acety1liflO- 4 (4'-trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetoxyImethyl) 2-pheny-fa1OfliC acid diethyl ester, 456 0 2(3-methOXycarbOflfifl0- 4 -trifJluorOflethyl- biphenyl-2-CarbOflYl) -amino] -phenyl}-aCetOXYmflthYl) 2- phenyl-malolic acid diethyl ester, trifluoromethYl-biPhefyl-l>CarbonYl) -amino] -phenyl)- acetoxymethyl)- 2-phenyl-malolic acid diethyl ester. 002-phenyl-(2-{6-[( 4 -trifluoromflthYl-bipheflYl- 2 V) carbonyl) -amino] I biphenyl-3-Y1}-aCetoxymethYl) inalonic acid o diethyl ester, 2 2 3 -formyl4[(4'-trifluoromethyl-biphenyl- 2 carbonyl) -amino] -phenyl)-aCetOXYImethYl) -2-phenyl-malonic acid diethyl ester. 2-C 2-(3-dimethylamiOrfethYl- 4 -trifluorornethyl- biphenyl-2-CarbOfl))-amino] -phenyl)-acetOxYflethYl) -2- phenyl-nalofliC acid diethyl ester, 2-(2-{3-Imethoxy-mthYlCarbalOYl) trifluoromethyl-biPheny> 2 -carbonyl) -amino] -phenyl) acetoxymethyl)-2-PhelYl-malOl±c acid diethyl ester, 2-I 3-isobutyryl-4- -trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyll-acetOXYImethY.) -2-phenyl-nalolic acid diethyl ester, and 2-(2-{3-(l-hydrcixy-2-methyl-propylV' 4 trifluoromethyl-biphelyl-2-carbOnYI) -amino] -phenyl)- acetoxynethyl) -2-phenyl-malorxic acid diethyl ester. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of (4-f -trifluoromethyl-biPhenYl-2-carbonYl) -amino] (N phenyll-acetic acid 2, 2-bis-ethylcarball2-PhenflethYl C) ester, (3-ethyl-4- -trifluoromflthYl-biphenfl 2 carbony)-ano~lO-phenyl)-acetic acid 2, 2-bis- ethylcarbamOyl-2-PhelYl-ethYl ester, [(4'-tilooety-lhny--abny)aio- 00 phenyl}-aCetic acid 2.phenyl2,2-bis-(2,22-trifluoro- Vn ethylcarbalnOyl)-ethyl ester, o -trifluoronmethyl-biPhefl-2-CarbonYl) -amnino] phenyll-aCetic acid 2, 2-bis-cyclOhexyCarbaflOYl- 2 phenyl-ethyl ester, -trifluoromnethyl-biphefl-l2-CarbonYl) -aimino) phenyll-acetic acid 2-pherlyl-2, 2-bis-phenylcarbJfl ethyl ester, W-trif luoromethyl-biPheflYl-2-CarbonYl) -aninol phenyll-acetic acid 2, 2-bis-isoprOpylCaramoyl-2-Phel- ethyl ester. 4' -trifluoromethyl-biphe1Y1-2-CarbOxcylic acid 4-112- phenyl-2, 2-bis- (2 ,2,2-trifluoro-ethy1CarbamOYl) ethoxycarbOlmthYJ-]-phenyl ester, biphenyl-2-carbOXYliC acid 4- [2-phenyl-2, 2-bis- (2,2,2 -trifluoro-ethYlcarbamOYl) -ethoxycarbolylfethyl] phenyl ester, [(biphenyl-2-carbOlYl) -amino] -phenylli-acetic acid 2-phenyl-?. 2-bis- 2-trifluoro-ethYlCarbmol)lethYl ester, 2-phenyl-2-(2-A2-trif1UOrOmfethYl- 4 (4- trifluoromethYl-biPhenfl1-2-CarbonYl) -amino] -phenyl)- acetoxymrethyJl)-malOflic acid diethyl ester, 0 {14- -trifluoromethy1-biPheylY2cabonYl) -amino] (1 pheriyl)-acetic -acid 2, 2 -bis -methYIcarb81lY2phenyl- ethyl ester, 4' -trifluorOmethy1-biPhflY2caboxylic acid 4- (2,2- bis-ethylcarbafoYl- 2 phenyl-ethoxyCarbOlJethYl) -phenyl ester. 00{4- -trifluorOflethYl-biPheflYl-2-carbonYl) -amino] ~phenyll-acetiC acid 2 ,2-bis- butylcarbamOY1-2 -phenl-ethyl o ester, (3-methyl-4-[(4' -trifluoromethYl-biPhenfll 2 carbonyl) -amino] -phenyll-acetic'' acid 2 ,2-bis- ethylcarbanOyl- 2-phenyl-ethyl ester, :trifluoromethyl'biphenyb-2-carbonYl) -arino] phenyl}-acetiC acid 3, 3-bis-ethycarbamfl-3-PhefYl-PrOPYl ester. -trifluoromethy1-biPhel12-Ca~rbonYl) -amino] phenyll -acetic acid 3 -phenyl- 3,3 -bis -propyloarbainoyl -propyl ester, [(biphenyl-2-carbOl) -amino] -phenyl)-acetic acid 2, 2-bis-ethylcarblfoYl-2-PheflYl ethyl ester, 4' -trifluoromethyl-biphefl2-crbOxcYlic acid 4- (2,2- bi-tycraol2pe y-toyabnlehl-2- chioro- phenyl ester, -trifluoromethy1-biphelyl-2-CarbOlYl) -amino] phenyl)-acetic acid 2,2-bis-iSObUtYlCarba1fOYl-2-PhenYl ethyl' ester, -trifluoromethyl-bipheny-2-CarbOflYl) -amino] phenyl)-acetic acid 2, 2 -bis 3-methyl -butylcarbafloYl) -2 phenyl ethyl ester. o1 4 4 Pchlorobiphely2-crboyl) -ainlo] phenfl) acetic acid 2,2-bis-ethyJ.C8rb8IylOY2PhenYl ethyl ester, 4 dichlorobiphey1..2-Carbonfl)-JliflO]' phenyl)-acetic acid' 2, 2-bis-ethylCarbamfoyl) -2-phenyl-ethYl ester, {3-methyl-4'-[(4' -trifluoromethY1-biPhnflY 00carbony1)-aminfl]Phenfl)l-aCetic acid 2-phenyl-2 ,2-bis- V) propylcarbamoYl)-ethYl ester, o -trifluoromethyl-biPhenfl-2-carbonYl) -amino]- phenyl-acetiC acid 2. 2-bis-(2-methoxY-thY1CrbImOYl) 2-phenyl--ethyl ester, {3-isopropy1-4- -trifluoromethYl-biPhelYl-2- carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbBoyJl-pheflJethYl ester, {3-ethyl-4- -trifluoronethY1-biPhelYl- 2 carbony1)-minfo]-Phefyl)lacetic- acid 3,3-bis- ethylcarbamflY>3-phenyl-prOpyl ester, {3-isobutyl-4-[ -trifluoromethY1-biPhelyl- 2 carbonyl) -amino]-pheny1)-acetic acid 2, 2-bis- ethylcarbaflOyl-2-PheflYl-ethYl ester, {3-dimethylcarbamfoYl-4- -trifluoromfethyl- biphenyl-2-carbOlyl)-amino] -phenyl)-acetiC acid 2-phenyl- 2, 2-bis-propylcarbamflY-ethYl ester, 3-methylcarbalfoy> 4 -trifluoromethyl-biPhel 2-carbonyl)-filO] -phenyl)-acetic acid 2, 2-bis- ethylcarbaTOyl-2-PheflYl-ethYl ester, 3-dinhethylcarbamfOYl- 4 -trifluoromethyl-biPhenfl 2-carbofl)-&filO]-phefylY1acetic acid 3,3-bis- ethylcarbaloyl -3 -phenyl -propyl ester, 0 (3-benzylcarbaiuoyl-4- -trifluprOmethyl-biPbelYl- 2 carbonyl)-aznino]-pheflyll-acetic acid 2,2-bis- ethylc arbamoyl- 2-phenyl-ethyl ester, (3-dirnethylcarbamoyl-4- -trifluoromethYl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetiC acid 4, 4-bis- ethylcarbamoyl- 4-phenyl-butyl ester, 0{ (3-diethylcarbamoyl-4- -trifluoromethyl-biphelYl- V)2-carbony)-8Ififlo]-pheflC-aCetic acid 2 ,2-bis- o ethylcarbalnoyl-2-pheflyl-ethYl ester. {3-diisopropylcarbamfly-4- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyll-acetic acid 2 ,2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, (isopropyl-nethylCarbafOYl) trifluoromethyl-bipheflyl-2-CarbOnYl) -amino] -phenyll-acetic acid 2,2-bis- ethylcarbamoyl-2-pheflYl-ethYl ester, (ethyl-methylcarbaloyl) -trifluorometlwl- biphenyl-2-carbOlyl)-amino] -phenyl)-acetiC acid 2, 2-bis- ethylcarbaxnoyl-2-pheflyl-ethyl ester, (ethyl-rnethylcarbafOyl) -trifluoromethyl- biLphenyl-2-Carbolyl) -amino] -phenyll-acetic acid 3,3-bis- ethylcarbamoyl-3 -phenyl-propyl ester, (piperidin-1-carboiyl) -trifluoromethyl- biphenyl-2-carbonyl) -amino) -phenyl)-acetic acid 2,2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, (pyrrolidin--carbonlY) -trifluoromethyl- biphenyl-2-carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbalnoyl- 2-phenyl-ethyl ester, (methyl-propylcarbanOyl) -trifitioroinethyl- biphenyl-2-carbOlyl) -amino] -phenylil-acetic acid 2,2-bis- ethylcarbainoyl-2 -phenyl-ethyl e ster, (methyl-propylcarbamfoyl) 4 41-trifluoromethyl- hiphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 3, 3-bis- ethylcarbamoyl-3-pheflyl-PrOPYl ester, {3-hydroxy-4- '-trifluoromethYl-biPhelYl-2- carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbalnoyl-2-PheflYl-BthYl ester, 3-methoxy- 4- '.-trifluoromethyl-biphel-2- carbonyl)-amino]-phelyl)-acetic acid 2,2-bis- ethylcarbamoyl-2 -phenyl-ethyl ester, {3-methoxy-4- -trifluoromethyl-bipheflyl-2- carbonyl) -amino] -phenyl)-acetic acid 2-phenyl-2, 2-bis- propylcarbamoyl-ethyl ester, {3-methoxy-4- '-trifluorornethyl-biphenYl- 2 carbonyl) -amino] -phenyl)-acetic acid 3, 3-bis- ethylcarbaxnOyl-3-pheflyl-PrOPYl ester, (3-ethoxy-4- -trifluoromethy1-biphel-2- carbonyl) -amino) -phenyl)-acetic acid 2, 2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, {3-ethoxy-4- -trifluorornethyl-biphenyl-2- carbonyl) -amino] -phenyl) -acetic acid 3' 3-bis-. ethylcarbaznoyl-3 -phenyl-propyl ester, {3-isopropoxy-4- -trifluoronethyl-biphelYl-2- carbonyl) -amino] -phenyl)-acetic *acid 2, 2-bis- ethylcarbamoyl- 2 -phenyl -ethyl ester, .{3-isopropoxy-4- -trifJuoromethyl-biPhelYl-2- carbonyl) -amino] -phenylli-acetic acid 3, 3-bis- ethylcarbwnoyl-3 -phenyl-propyl ester, {3-propoxy-4- -trifluoromethyl-biphelyl-2- 462 Ocarbony1)-8lifl-pheylY1>aCetic acid 2,2-bis- o ethylcarbamOy1-2-phenfl-lthYl ester, (3-benzylOXy-4- 1(4' -trifluoromethY1-biPheflYl- 2 carbony.) -amino] -phenyJ}-aCetiC acid 2, 2-bis- ethylcarbamOy1-2-Phenfl>thYl ester, {3-dimethylaminfO-4- -trifluorOmethY1-biPheflYl-2 00carboflyl) -amino) -phenyl)-acetic acid 2, 2-bis- ethylcarbalOyl- 2-phenyl-ethyl ester, o (3-piperidifl-1-yl- 4 -trifluoromethY1-biPhelYl- 2 carbonyl) -amino] -phenyll-aCetic acid 2, 2-bis- ethylcarbamOyl- 2 -phenyl-ethyl ester, 3-pyrrolidifl-1-yl- 4 -trif luorOmethiYP-biPhelYl- 2-carbonyl) -amino] -phenyl)-acetic acid 2. 2-bis- ethylcarbamOyl-2-pheflYl-BthYl ester, (3-1(4'-~trifluoromethy1-biPhefl12-CarbonYl) -amino] phenyl)-acetic acid 3, 3-bis-ethylcarbaXoy1-3-Phel-PrOPYl ester, [(4'-~trifluoromethy1-biphefl-2-CarbOnYl) -amino) phenyl) -acetic acid 3-phenyl-3, 3-bis -propylcarbamoyl- propyl ester, -trifluoromethy1-biPhenfl-2-carbOnYl) -amino] phenyl)-acetic acid 3, 3-bis-isopropycrbaml-3-PheflYl- propyl ester, (2-Inethyl-3- -trifluoromethyl-biPhenyl- 2 carbonyl) -ami-no 3-phenyl)l-acetic acid 3,3-bis- ethylcarbamoyl- 3-phenyl-propyl ester, (2-methyl-3- -trifluoromethy1-biphenYl- 2 carbonyl) -amino] phenyili-acetic acid 4,4-bis- ethylcarbafoyl- 4-phenyl-butyl ester, {2-methyl-3- -trifluoromethYl-biPhenfl-l> C) carbonyl)-afifl]- phenyl)-acetiC acid 3-phenyl-3, 3-bis- propylcarbainoyl-propyl 'ester, (2-znethoxy-3- -trifluoromethyl-biPheflYl-2 carbonyl)-aliflO]- phenyl)-aCetiC acid 3 ,3-bis- ethylcarbamoyl-3 -pheriyl-prOpyl ester, 00 (2-ethoxy-3- -trifluoromethYl-biPhelYl- 2 in carbonyl) -amino] phenyl}-a.Cetic acid 3, 3-bis- o ethylcarbafoYl- 3 -phenyl-propyl ester, 4- -trifluoromethyl-biPhefl-2-CabonYl) -amino] benzoic acid 3,3-bis-ethylCarbamrOY1-3-Phefl1ProPYl ester, 4 -trifluoromethyl-biPheyl-l2-caboxcylic acid 4- (3,3- bis-ethylcarbalfOYl-3 -phenyl-propoxycarbOfYl) -2 -chioro- phenyl ester, 4 -triflnoromethyl-biPhenyl2-CarboxWlic acid 4- (3,3- bis -ethylcarbafoYl-3 -phenyl-propOxycarbolYl) -phenyl, ester, 4' -triiluorornethyl-biPhefl> 2 -carboxylic acid 4- (3,3- bis-ethylCabamfOyl-3-PhelYl-PrOoxycarbonYl) -2 ,6-dichloro- phenyl ester, 5- (2,2 -bis-ethylcarbafoyl- 2-phenyl-ethOXyCarboflYl- methyl) -trifluorOmethYl-biPhelYl-2-CrbolYl) amino] -benzoic acidbenzyl ester, (2,2bsehlabmy -pey-toyabnl methyl) -trifluoromethYl-biPhefl12-CarbonYl) aznino)-benzoic acid, (2,2-i-tycramy -hnletoyabnl methyl) -trifluorometbYl-biphelyl carbonyl) aminol-benzoic acid ethyl ester, and 2-bis-ethylcarbamoyl-2-pheflyl-ethOxWCarbonyl' methyl) -trifluoromethyl-biphefl-2-C8abOnYl) C) arinoJ-benzoic acid methyl ester. ci 26. The ester compound or a prodrug thereof, or a 0 5 pharmaceutically acceptable salt of either according to claim 1,'which is selected from the group consisting of Ic) carbonyloxy) -phenyl] -acetoxymethyl)-falOfic acid diethyl o ester, 2- (2-{3-rnethyl-4- -trifluoromethy.-biPheflYl- 2 carbonyl) -amino) -phenyl}-acetoxyfethYl) -2-pheny--maloflic acid diethyl ester, 2- [iethyl-(4 -trifluoromethYl-biPhenYl- 2 carbonyl) -amino] -phenyll-aCtoxyflethYl) -2-phenyl-ma-ofliC acid diethyl ester. 2-hnl2(-4-( tilooety-ihnl2 carbonyl) -amino -phenyij'-acetOxyfethYl) -malonic acid diethyl ester, 2-phenyl-2- -trifJluoronmethyl-biPhenYl-- 2 carbonyl) -amino] -phenyl) -acetoxyinethyl) -malonic acid diisopropyl ester, 2-phefyl-2-(2-{ 4 4 -trifJluoromethyl-biPhefl- 2 carbonyl) -amino] -phenyl)-acetOx-Ylfethyl) -malefic acid dimethyl ester, 2-cyclopentyl-2-(2-{ 4 -trifluoromethYl-biphel- 2-carbonyl) -amino] -phenyl}-acetoxyfethyl) -malonic acid diethyl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) -amnino] -phenyl)-aCetoxymethYl) -malonic acid 0 dicyclohexyl ester, 2 -befzl-y2(2d(4E(4trifluoromethYl-biphenyl-2 carbonyl) -amino) -phenyll -acetoxymethyl) -malonic acid diethyl Mn C] ester, 2- (2-{2--fetyl4-[ (4'-trif luOrOmelthy1TiphnflY1> V carbonyl) -amino] -phenyl}-aCetOXYmrethY-) -2-phenyl-malonic 00 acid diethyl ester. o 2-carbonyl) -amino] -phenyl}-acetOXYflethYl) -malonic acid diethyl ester, 2-pheny1-2-(2-{2-trif1uoromethyl- 4 4 trifluoromethyl-biphel>2 -carbonyl) -amino] -phenyl)I- acetoxymethyl)-nalOliC acid diethyl. ester, 2-pyridil-2-Y3.-2- 4 (4'-,trif luorOmfethyl-biphefl 2-carbonyl) -amino]I-phenyl}-acetOXYfllthYl) -malonic acid diethyl ester, 2-yii--l2(-4-('tilooehl biphenyl-2- carbonyl) -amino] -phenyl)-acetOXYlfethYl) malonic acid diethyl ester, 2-pheny1-2-(2-{3-trif1uoromthyl-4L[( 4 trifluoromethy1-biPhel2-CabolYl) -amino] -phenyl)- acetoxymethyl)- malonid acid diethyl ester, 2- 4- -methyl-biphelyl-2-carbolYl) -amino] phenyl)-cetOXYflethYl) -2-pheny--maloflic acid diethyl ester, 2-2(-('mtoybpey--abnl-mn] phenyll -ace toxymethyl) 2 -phenyl -malolic acid diethyl ester, 2-phenyl-2 -trifluoromethyI-biPhel-2- carbonyl) -amino] -phenylhl-acetoxymfethYl) -malonic acid diethyl ester, 0 2- [isopropyl-( 4 -tritluoromethY1-biPhnyl o ~carbonyl) -amino) -phenyll -acetoxyinethyl) -2 -phenyl-ma-loliC acid diethyl ester, ci 2- (2-f 4- [cyclohe)Cyl-( 4 '-trifluoromethY1ThiPhenYl->- carbonyl) -amino] -pheny1)-aCetOXYflethYl) -2-pheny-fa1OfliC acid diethyl ester, 00 00 2 -phenyl 2 (2441(4-trifluoromethYl-biphenyl- 2 Vci carbonyl) -amino] hnl-ceoyehl-malonic acid o dipropyl ester, 2-phenyl-2-(2{( 4 4 -trifluoromfethyl-biphenyl- 2 carbony-) -amino] -phenyl) -acetoxyroethyl) -malonic acid diisobutyl ester, 2-(2-{4-[Sthyld(4 -trifluoromthy1-biPhnflY carbonyl) -amino] -phenyll -acetoxymethyl) -2-pheny1-ma1OliC acid diethyl ester, 2-(2-f3-ethyl-4-L (4'-trifJ-uorOmfethYl-biPhenYl-2> carbonyl) -amino] -pheny1)-aCetOXYmfethYl) -2-phenyl-malolic acid diethyl ester, 2-2(-spoy--('trfurmty-ihnl2 carbonyl) -amino I-phenyl) -acetoxyinethyl) -2 -phenyl-maOliC acid diethyl ester, 2-(2-{3-iSObutyl-4-[(4'-trifluorOJmethY1-biPhefl- 2 carbonyl) -amino] -pbeny1)-aCetOXYmfethYl) -2-pheny1-ma1OfliC acid diethyl ester, 2-(2-{3-Ch1r0-4E (4'-trifJluorOmlethY-biphefli 2 carbonyl) -amino] -pheny1)-aCetOXYmlethYl) -2-phenyl-maloflic acid diethyl ester, 2-2[-rm--('tifurmty-ihnl2 carbonyl) -amino]-~pheny1}-aCetOXYmethYl) -2-pheny-maOliC 0 acid diethyl ester, 2-{3-dilethy1C8arbamflY-4- -trifluoromrethyl- biphenyl-2-CarbolYl) -amino] -pheny1)-aCetOXYfllthYl) -2- phenyl-nSlOfliC acid diethyl ester, 2- 2-{3diethy1CarbamOYl- 4 -trifluorometll- V biphenyl-2-CdLrbOlYl) -amino) -pheny1)-aCetOXYmfethl)-2- 00 phenyl-malOflic acid diethyl ester, 2 -(2-{3-diisopropylcarbamnoYl- 4 -trifluoromethyl- o bipheny-2-C8.rbofl)Yflil] pheny1J-aCetOXYmflthYl)- 2 phenyl-maloliC acid diethyl ester, 2 -c 2 3 -(ethy1-methy1carbaoloY)-4[(4-trifluoro- rnethy1-biphefl-2-CarbolYl) -amino]-~pheny1)-aC etOXYrflthYl) 2-phenyl-malOnic acid diethyl ester, (pyrroidine-1-carbolyl) -trifluoromethy- biphenyl-2-CarbOlyl) -amino] -phenyl}-aCetiC acid 2 ,2-bis- ethylcarbamroYl -2 -phenyl-ethy. ester, 2-hnl2(-3(yrldn--abnl--(' trifluoromethYl-biPhenYl-2cabonYl) -amino] -phenyl)- acetoxymethYl)-maloliC acid diethyl ester, 2-hnl2(-3(ierdn--abnl trifluoromethY1-tiPhenY-2cabonYl) -amino] -phenyl 1- acetoxynethyl)-laloflic acid diethyl ester, 2- (2-{3-dimethylcarbafOyl- 4 -trifluoro- methyl-biphenyl-2-CarbOl) -amino] -phenyll -acetoxy)- ethy1]-2-peny-fa1ofliC acid diethyl ester, 2- (2-{3-dimethy1CarbamOY1- 4 -trifluoromfethyl- biphenyl-2-CarbolYl) -amino] -pheny1)-aCetox-YmfethYl) -2- phenyl-maloflc acid diethyl ester, 2-2 -('boobpey--abnl-mn]3 468 o ajdsnethylcarbaxnoY1-PheflI -aCetoxcYmethYl) 2-pheny1-na1Oflic acid diethyl ester, 2- (2-{3-dinethy1CarbamollOY 4 -trifluorOmethyl- Ci biphenyl-2-carbOflYl) -amino] -pheny1}-aCtOX-YflethYl) -2- phenyl-faloflic acid diethyl ester, 2 -carbonyl) -amino] -phenyl- acetoxymethyl)-malOlic acid diethyl ester, acddehy se, trif2uoroethY1'bi el-2lhl2carbony -ami -h ny)-- aeoxyehi )flaoi acid diethyyl ester, 3drnethylCarbafOYl-Phe l-acetoxymethyl) -2-pheny- fi mlcacid diethyl ester, 3-2-3dimethYJlarbamOYPel1aeocyl-[(eth)--eyl- actxyehl--hnlmalonic acid diethyl ester, dimethorbaflOYJiPhefylY1>aetonW1lethal phenyl)- xyehl)2phnlmalonic acid diethyl ester, 2 -[(2{3diethycarbThoy1-4-(4etfluooehl tiformehYnbyhfl12-carbonl) -amino] -phenyU)aeoy-rpl-2 aeoyhl-2phenyl-maloflic acid diethyl ester, o ~2.(23dimthy1cir8YJ-W ehxy- 4 trifluoromethyl-biphelYl- 2 -carbonyl) -amino] -pheny- acetoxyznethyl)-2-PhefllmalOfliC acid diethyl ester. carbonyl) -amino] dimethycarbaUOY-PhelI- acetoxymethy)-2-Phel-maloliC acid diethyl. ester, 00 2-(2-{3-dimethy1carbamolOy4[(6-Wethyl- 4 trifluoromethyl-biPhelYl-2-CarbOflYl) -amino] -phenyl)- o acetoxymethyl)-2-PhelYl-falOfliC acid diethyl ester, 2- (2-{3-dimethylcarbafOYl-4-[14' -trifluoromethyl- biphenyl-2-carbolyl) -amino] -phenyll-acetoxymfethYl) -2- phenyl-malonic acid di-2, 2.2-trifluoroethyl ester. 2-(2-{3-dimethylarbafOYl-4-[ (2'-fluoro-C'- trifluoromethyl-biphenyl-2-CarbolYl) -amino I-phenyl) acetoxymethyl)-2-phel-malolic acid diethyl ester, 2-(2-{5-dimethylcarbamOY1-2-f1UOro- 4 trifluoromethyi-biphenyl-2-carbOlyl) -amino] -phenyl)- acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-(2-{3-bromo-5-dilethYcarbmoYl 4 trifluoromethyl-biphelyl-2-carbolYl) -amino I-phenyl)- acetoxynethyl)-2-phenyl-a.OfiC acid diethyl ester, 2-(2-{3-chloro-5-dimethY1CarbakUoy1-4[(4'- trifluoromethyl-biphenyl-2-carbonYl) -amnino] -phenyl)- acetoxymethyl)-2-phenYl-laloflic acid diethyl ester, 2-(2-{3-dimethylcarbamol-4-i(3'-f1uoro- 4 trifluoromethy1-biphenY-2CarbolYl)-amino] -phenyl)- acetoxyethyl)-2-phelyl-laloflic acid diethyl ester, (3'-chloro-4'-trif1UorONmethYJ.-biPhefl-l 2 carbonyl) -amino 1-3 -dimethylcarbamoyl-phenYI) 470 acetoxymethy)-2-PheflYl-malonic acid diethy. ester, (2-{3-dimethylcarbafoyl- 4 '-trifluorOmfethyl- bipheny-2-CarbOflYl) -amino] -phenyl)-acetOxYmethYl) -2-C ci nitro-pyridin-2-Yl)hmalofliC acid diethyl ester, -trifluoromethYl-biPhel-2-CarbonYl) -amino] -phenyl)- 00 acetoxymethyl)-falOfliC acid diethyl. ester, In (2-{3-dimethycarbamfl- 4 -t -trifluoromfethyl- o ~biphenyl-2-CarbOlYl) -amino] -phenyl)-aCetOxYflethyl) -2- pyridiLn-2-y-falOfliC acid diethyl. ester, 2- (3-chioro- 5-dimethylcarb5ImOy1-2-flUOrO- 4 -trifluoromethy1-biPhefylY1>cabonyl) -amino] -phenyl)- acetoxyrnethy1)-2-Phelyl-malonic acid diethyl ester. 2-2{-rm--iehlabmy--loo4 -trifluoromethY1-biPhefl2-CarbonYl) -amino] -phenyl) acetoxymfethY)-2-Pheyl-lmalonic acid diethyl ester. 2-C 2-{3-dixnethylcarbafoyl-4- -trifluoromethyl- biphenyl-2-carbolYl) -amino] -pheny1)-acetoxflethYlP- 2 -o- tolyl-malolic acid diethyl ester, 2-(3-dimethylcarbafOyl- 4 -trifluoromethyl- biphenyl-2-carbolYl) -amino] -phenyJ.)-acetoXYmethYl) -2-r- tollyl-malonic acid diethyl ester, 2- (2-{3-dirnethylcarbaffl-4- -trifluorornethyl- biphenyl-2-carbolYl) -amino] -phenyl}-acetoxymethYl)- 2 -P tolyl-malonic acid diethyl ester, 2-3clr-hnl--(-(-Jmtycraol4 -trifluoromethY1-biPhefl-2-CarbonYl) -amino] -phenyl)- acetoxymethyl)-falonic acid diethyl ester, 2-3clr-hnl--2-3dmtycraol4 0 '-trifluoromethy1-biPhefyl-l2-crbonYl) -amino] -phenyl}- acetoxymethyl)-ma1ofliC acid diethyl ester, -trifluorornethy1-biPhefl2-carbonYl) -amino] -phenyll- acetoxymethyl)-malOflic acid diethyl ester, (2-(3-dimethy1CarbamOY1-4- -trifluoromethyl- 00 biphenyl-2-CarbOlYl) -amino] -phenyll-acetosylethYl) -2- phenyl-succiliC acid diethyl ester, o ~2-(2-{3-dirnethylcarbamfOYl- 4 -trifluoromethYl- biphenyl-2-CarbOlYl) -amino] -phenyl)-acetoxYmethYl) (2- methoxy-phenyl)-malOnic acid diethyl. ester, 2-(3-diznethyloarbamfOyl- 4 -trifluoromet Yl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetOxymethyl) (3- methoxy-phenyl) -malonic acid diethyl ester, 2- (2-{3-dimethylCarbImOyl-4-[(4' -trifluoromethy- biphenyl-'2-carbOlYl) -amino] -phenyll-acetOXYflethYl) (4- methoxy-phenyl)-falOlic acid diethyl ester, -bis-trifluoromethy1-biPhelYl- 2 carbonyl) -amino] -3-diniethylcarbamfOYl-PheflYl) acetoxymethyl)-2-phey-alOfliC acid diethyl ester, (6-chloro-4'-triflUOromethY1-biPhenflYJ 2 carbony.) -amino] -3 -dixnethylcarbdinoyl-Phefl)I- acetoxymnethyl) -2-phenyl) -malonic acid diethyl ester, 2-(2-{3-dimethy.carbamOYl- 4 (G-fluoro-4'- trifluoromethyl-biphel-2-carbonyl) -amino] -phenyl) acetoxymethyl) -2-phenyl) -malonic acid diethyl ester, 2- (2-{3-dimethy-carbwfloYl-4- [(5-methyl-4' trifluoromethyl-biphelyl 2-carbonyl) -amino] -phenyl) acetoxy) -ethyl] -2-phenyl) -malonic acid diethyl ester, 472 O2-(2-{3-dimethy1Carbamoy-4[(5ethoxy- 4 o trifluoromethYJl-biPbhflYl- 2-carbonyl) -amino] -phenyl) acetosymethy)-2-Phel)-malOnic acid diethyl ester, 2-(2-{3-dimethy1carbwnolY-4-[(5isoprOPOx- 4 trifluoromethY1-biPhefl-2-CaxbonYl) -amino] -phenyl) acetox-ymethy)-2-Phel)IfalOnic acid diethyl ester, 00 2-2(-4[54-i-rfurmty-ihnl2 Ncarbonyl) -amino] -3 -dimethylcarbalfOYl-Phefl}-acetoxy) o ethyl)-2-PieflYl-malOflic acid diethyl ester, trifluoromethyl-biPhel-2-carbonyl) -amino) -phenyll acetoxyrnethyl) -phenyl-maloflic acid diethyl ester, 2-(2-{3-dimethy1carbaoy-4(3-methyl> 4 trifluoromethy1-biPhefylyb2carbOnYl) -amino] -phenyll- acetoxymethyl)-2-PhelYl-malOfliC acid diethyl ester, 2-2[-24bstllormty ezyaio-3- dimethylcarbanoyl-PhenYl] -acetoxymethyl}-2-PhelYl) -ialonic acid diethyl ester, 2- (2-f 3-dimethylcarbamflJ-4- -methyl-biphenyl-2- carbonyl) -amino] -phenyl)}-aceto-YlfethYl) -2-phenyl-mal-oflic acid diethyl ester, 2-2[-iehlabmy-4[2ehl4tiloo rnethyl-benzOYlamilo) -phenyl] -acetoxymethy-)-2-Phenfl- malonic acid diethyl ester, 2-2(-iehlabmy-4[4-ty-ihnl2 carbonyl) -amino] -pheny1}-acetoxyltthYl) -2-phenyl-malonic acid diethyl ester, 2- (2-{3-dimethylCarbamoyl-4- -isopropenyl- biphenyl-2-CarbonYl) -amino] -phenyl) -acetoxymethyl) -2- 473 phenyl-maloflic acid diethyl ester, 0) 2-(2-{3-dimethy1CarbamhOY1-4- -isopropyl-biphenyl- 2-carbonyl) -amino] -pheny1)-actOXYmfethYl) -2-phenyl-malOflic acid diethyl. ester, [3-dirnethylcarbafoyl- 4 -trifluoromethyl- -bipheny1-2-carboflOXY)-phenyl] -acetoxmethy1}-2-phel- malonic acid diethyl ester, V')2-(2-{3-dimethylcarbafOYl- 4 -trifJ-uoromethyl- o ~biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetOXYmfethYl) -2- thiophen-2-yl- malonic acid diethyl ester, (2-{3-dimethylCrbamfOYl> 4 -trifluorometh-yl- biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetOXYmethYl) -2- thiophen-3-yl- malonic acid diethyl ester, 2- (2-{4-dimethylcarbalOyl-5- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino) -pyridin-2-y1)-aCetOXY1TethYl) 2-phenyl- malonic acid diethyl ester, 2- (2-{3-dimethycarbamfOYl- 4 -trifluoromethyl- biphenyl-2-cabOlYl) -amino] -pheny11-acetOXYmethYl) (3- methy1-thiophel-2-Y1)-malOflic acid diethyl ester, 2- (2-(3-dimethylcarbflOyl- 4 -trifluoromethyl- biphenyl-2-carboiYl) -amino] -phenyl)-acetoxyTmkthYl) methyl-thiophefl-2-Yl) -malonic acid diethyl ester, 2- (2-{3-dimethylcarbamfl- 4 -trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyl)-acetoxYmfethYl) -2- thiazol-2-y-naloflic acid diethyl ester, 2-(2-{3-ethoxy-4-[ (4'-trifluorOmfethyl-bipheflYl-2- carbonyl) -amino] -phenyl}-acetOxyfethyl) -2-phenyl-malofic acid diethyl ester, 2-C 2-{3-methoxy-4- -trifluoromethyl-biphelyl- 2 CI carbonyl) -amino] -phenylj-aCetoxymfethYl) -2-phenyl-malOfliC C) acid diethyl ester, 2-(2-f3-iSCoprOpOxy-4- -trifluoromethy1-biPhel 2-carbonyl')-amino) -phenyl}-acetOXymfethYl) -2-phenyl-maloflic o 5 acid diethyl ester, 2-(2-{3.-benzylOXy-4-[ (4'-trifluorOmethyl-bipheflYl- 2 00 carbonyl) -amino] -phenyll-acetOxyfethyl) -2-phenyl-malofliC V) acid diethyl ester, o 2-(2-{3-hydroxy-4-[ (4'-trifluoromethY1-biPhel-2- carbonyl) -amino] -phenyl)-acetoxyfethYl) -2-phenyl-malonic acid diethyl ester, 2-f 2-[3-methoxy-4-E -trifluoromethyl-biPhefyll2- carbonyloxy) -phenyl] -acetoxymethyl) -2 -phenyl-malonlc acid diethyl ester, 2-hnl2(-3pprdn1y--('tiloo methyl-biphenyl- 2-carbonyl,)-amino] -phenyl)I-acetoxymethyl) inalonic. acid diethyl ester, 2-phenyl-2- (2-f 3-pyrrolidin-1-yl-4- -trifluoro- methyl-biphenyl-2-CarbolYl) -amino] -phenyl)-acetoxymflthYl) mualonic acid diethyl ester, 2- (2-f 3-dimethylano-4- -trifluorornethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxyfethY.) -2- phenyl-malolic acid diethyl ester, 2-C 2-f3-morpholifl-4-y1- 4 '-trifluoromethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxYmfethYl) -2- phenyl-malolic acid diethyl ester, 2-C 2-f3-diethylamilo-4- -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyl}-acetoxyfetbyl) -2- phenyl-maloflic acid diethyl ester, (N 2-[2-(2-{2-methyJ--3-( (4'-~trifluoromethyl-biPheflYl- 2 carbonyl) -amino] -phenyl}-aCetOXY) -ethyl] -2-phenyl-maloflic acid diethyl ester, carbonyl) -amino] -phenyl)-acetOXYmfethYl) -maloflic acid diethyl ester, 0 o diethyl ester, carbonyl) -amino] -phenyl) -acetoxy) -ethyl] -2-phenyl-malOflic acid diethyl ester, 2-t2-(2-(2-methYl-5-[ (4'-trifuoromlethyl-biPhefl 2 carbonyl) -amino] -phenyll-acetoxy) -ethyl] -2-phenyl-faloflic acid diethyl ester, 2 2 2 2 methoxy-3(4-trifluoromethyl-biphenYl- 2 carbonyl) -amino] -phenyll-acetoXY) -ethyl] -2-pheflyl- malonic acid diethyl ester, 2-2(-2ehx--('trfurmty-ihnl2 carbonyl) -amino] -phenyll-aCetoxy) -ethyl] -2-phenyl-malolic acid diethyl ester, 2-2(-2iorpx--('tilooehl biphenyl-2-CarbOnYl)-amil]-phenyl}-acetoxy) -ethyl]-2- phenyl-malolic acid diethyl ester, 2-(2-{2-miethoxyCarboflYl-3-[(4' -trifluoroinethyl- biphenyl-2-carbOlYl) -amino] -phenyl)-acetoxy) -ethyl]-2- phenyl-nalOflic acid diethyl ester, 2-2(-2ehx--ehl--('tilooehl biphenyl-2-carbOflYl)-amino] -phenyl}-aecetoxy) -ethyll-2- (N phenyl-malolic acid diethyl ester, 2-phenyl-2- '-trifluoromethy1-biPhelYl- 2 carbony.) -amino] -benzoyloxy)-8thY1] -malonic acid diethyl ester., 0 2-(2-{3-methyl-4-[(4' -trifluoromtthY1-biphenfl-l' carbonyl) -amino] -benzoyloxyl-BthYl) -2-phenyl-malolic acid diethyl ester, o ~carbonyl) -amino] -benzoyloxy)-ethyl) -2-phenyl-falOflic acid diethyl ester, carbonyloxCy) -benzoyloxy] -ethyl-mfalOfliC acid diethyl ester, 2-(2-{3-ethoxyCarbOl- 4 -trifluoroinethyl- biphenyl-2-carbOlYl) -amino] -phenyl}-acetOxYlfethyl) -2- phenyl-mfalOflic acid diethyl ester, 2- (3-{3-dimethylarbamfOyl- 4 -trifluoromethyl- biphenyl-2-carbOlyl) -amino] -pheny1)-prOpiOloxymethYl) 2-phenyl-maloflic acid diethyl ester; 2-(2-{3-beflzylOXyCarbOflY 4 -trifluoromethy- biphenyl-2-CarbOlYl) -amino] -pheny1)-acetOSYflethYl) -2- phenyl-inalonic acid diethyl ester, 2-2{-abx--('tifurmty-ihnl2 carbonyl) -amino] -pheny1}-actOXYflethYl) -2-phenyl-malolic acid diethyl ester, 2-(2-{3-iSOprOPOXYCarbOl>4-[(4' -trifluorornethyl- biphenyl-2-carbOflYl) -amino] -pheny1)-aCetoxyrfethYl) -2- phenyl-maflic acid diethyl ester, 2-{3-methoxyCarbofl14- -trifluoromethyt- biphenyI-2-carbOfl) -amino] -pheny1)-acetoxymethYl)- 2 CI phenyl-malonic acid diethyl ester, O1 2-(2-(3-acetylalnfO- 4 -trifluoromethY1-biPhel- 2-carbonyl) -amino] -phenyl}-acetOxYflethyl) -2-phexyl-lalOfliC acid diethyl ester, 2-t3-methoxyCarbOlamiflo- 4 -trifluorOinethyl- biphenyl-2-carbOlll-amino] -phenyl)-acetOXYmfethyl) -2- 0 o ~methyl-biphenyl-2-Carbolyl) -amino] -pheny1)-acetOKYmfethYl) 2-phenyl-malonic acid diethyl ester, carbonyl) -amino) -bipheny1-3-y11-acetoxymethYl) -malonic acid diethyl ester,. 2-2(-oml4[4-rfurmty-ihnl2 carbonyl) -ami-no] -phenyll -ac-etoxymethyl) -2 -phenyl-malonic acid diethyl ester. 2- (2-{3-dimethylaminomfethYl- 4 -trifluoroinethyl- biphenyl-2-CarbonYl) -amino] -phenyl)-aCetOXYmfethYl) -2- phenyl-malonic acid diethyl ester,. 2-2(-mto--ehlaraol--('tiloo zethyl-biphenyl-2-Carbonyl) -amino] -phenyl) -acetoxymethyl) 2-phenyl-malonic acid dietbyl ester, 2-(2-{3-isobUtyryl-4-[ (4'-trifluoromethyl-biphelYl- 2-carbonyl) -amino] -phenyl)-acetOXymTethYl) -2-phenyl-malonic acid diethyl ester, and 2-(2-(3-(1-hydroxy-2-methy-propylh 4 4 trifluorornethy1-biphel-2-CarbOnYl) -amino] -phenyl)- acetoxynethy1)-2-Phe1y1laflic acid diethyl ester. 478 (N 27. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of -trifluororfethylbiPhnYl>2-carbonYl) -amino] 0 5 phenyli--acetic acid 2, 2 bis -ethylcarbamoflY2 -phenyl -ethyl ester, {3-ethyl-4- [(4'-~trifluoroxethYl-biPhenYl-2-CarbolYl) amino] -phenyll-acetic acid 2, 2-bis-ethylcarbaUOYl-2- o pheriyl-ethyl ester, -trifluoromethyl-bipheflYl-2-arbOnYl) -amino] phenyl}-acetic acid 2-phenyl-2,2-bis-(2,2,2-triflUoro- ethylcarbaflOYl) -ethyl ester, -trifluoromethyl-bPhelYl-2-carboflYl) -amino] phenyll-acetic acid 2 ,2-bis-cyclohexy1CarbamOYl-2- phenyl-ethyl ester, -trifluoroznethyl-bipheflYl-2-carbOnYl) -amino] phenyll-acetic acid 2 -phenyl- 2, 2 -bis -pheflylCarbamoyl- ethyl ester, 4- '-trifluoromethyl-biPbenYl-2-CarbonYl) -amino] phenyll-acet-ic acid 2, 2-bis-isopropylcarba1fOYl-2- phenyl-ethyl ester, [(biphenyl-2-carbolYl) -amino] -phenyl)-acetic acid 2-phenyl-2, 2-bis- (2,2 ,2-trifluoro-ethylCarbamOyl) -ethyl ester, 2-hnl2(-2tiloomty--('tiloo methyl-biphenyl-2-CarbonYl) -amino] -phenyl}-acetoxyfethYl) malonic acid diethyl ester, -trifluoromethyl-biPhenyl2-CarbonYl) -amino] phenyl}-acetic acid 2, 2 -bis-mnethylcarbamfoyl- 2-Phefl -ethyl ester, [(4'-~trifluoromethyl-biPheflJ2-CarbonYl) -amino] phenyl}-acetic acid 2, 2-bis-butylcarbamOYl-2-PhelYl-ethYl ester, o 5 {3-methyl-4- -trif2luoromethyJ--biPheflJ2 carbonyl) -amino] -phenyl)-acetic acid 2,2-his-ethyl- 00 '4 carbamoyl-2-pheflyl-ethYl ester, 0' trifluoromethy1biphefl2-carbonYl) -amino] o phenyl)-acetic acid 3, 3-bis-ethylcarbamOY1-3--Phefyl-lPropyl ester. -trifluoromethyl-bipheflYl-2-CarbOnYl) -amino] phenyll-acetic acid 3-phenyl-3, 3-bis-propyl- carbancyl- propyl ester, (biphenyl-2 -carbolyl) -amnino] -phenyl) -acetic acid 2, 2-biLsethylcarbamlOyl-2-phenflYethYl ester, (4-lI(4' -trifluoromethyl-biPhel-2-CarbonYl) -amino]- phenyl)-acetic acid 2, 2-bis-isobutylCarbamflO2lphefl ethyl ester, -trifluoromethyl-biphelYl-2-CarbOflYl) -amino] phenyl)-acetic acid 2, 2-bis- (3-methy1-buty1CarbamOYl) -2- phenyl-ethyl ester, clr-ihny--abnl-m''n]pey acetic acid 2. 2-bis-ethylcarbamOYl-2-Phefl-lthYl ester, -dichloro-~biphenyl-2-carbOflYl)-IminO]- phenyl)-acetic acid 2, 2-bis-ethylcarbwfoyl-2-PheflYl-ethYl ester. {3-methyl-4- -trifluorozethy-biPhenYl- 2 carbonyl) -amino]-phenyl}-acetic acid 2-phenyl-2. 2-bis- propylcarbamoyl-ethyl ester, (N -trifluorOmfethy1-biPhenfl2caZboflYl) -amino] phenyl)-acetic acid 2. 2-bis-( 2-methoxy-8thY1Carbafl) 2-phenyl-ethyl ester, (3-isoprOpyl- 4 -trifluoromethYJl-biPheflYl-2- 0 5 carbonyl) -amino] -phenyll-acetic acid 2, 2-bis-ethylcarbaloyl- 2-phenyl-ethy- ester, {3-ethyl-4- -trifluoromlethY1TiPhenYl- 2 V carbonyl)-aflfo] -phenyl)-acetic acid 3 ,3-bis -ethyl- o carbanoy1-3-Phel-lProPYl ester, (3-isobutyl-4- -triflnoromethy1-biPhelYl- carbonyl)-amil]-phenyll-acetic acid 2, 2-bis -ethyl- carbanmoyl-2-pheyl-lethYl ester, (3-dimethylcarbamoYl- 4 -trifJluoroiethY1- biphenyl-2-CarbOlYl) -amino] -phenyl)-aCetiC *acid 2-phenyl- 2, 2-bis-propy1CarbamfOYl-6thYl ester, {3-methylcarbalOYl- 4 -trifluoromfethyJl-biPhefl 2-carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbamflY 2 -phenyl-ethyl ester, (3-dimethylCarbwflOyl- 4 -trifluoromethyl- biphenyl-2-CarbolYl) -amino] -phenyll-acetic acid 3. 3-bis- ethylcarbal-l3 -phenyl-propyl ester, (3lbenzylcarbamfoyl-4- -trifluoromethyl-biphelyl- 2 -carboflyl)-aflifolOPhefl)l-acetic acid 2,2-bis- ethylcarbarnoyl- 2-phenyl-ethyl ester, {3-diznethylCarbalOYl-4- -trifluoromethYl- biphenyl-2-CarbOll) -amino] -phenyJl1-aCetiC acid 4, 4-bis- ethylcarbafOyl- 4 -phenyl-butyl ester, {3-diethylcarbalOYl- 4 -trifluoromethyl-biphelyl- 2-carbonyl)-amfifol-fPhefl)l-acetic acid 2,2-bis- 481 0 etbylcarbamoyl- 2-phenyl-ethyl ester, {3-diisopropylcarbamOyl-4- -trifluoroinethyl- biphenyl-2-carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, (isopropyl-methylcarbafloyl- 4 '-trifluoro- V) methyl-biphenyl-2-CarboflYl) 00 amino] -phenyl)-acetic acid 2, 2-bis-ethylcarbamoyl-2- phenyl-ethyl ester, o f3- (ethyl-methylcarbamOyl- 4 -trifluoromethyl- biphenyl-2-carbolyl) -amino] -phenyl)-acetic acid 3, 3-bis- ethylcarbamoyl- 3-phenyl-propyl ester, (piperidine-1-cabolyl) -trifluorometbyl- biphenyl-2-carbol)-amino] -phenyl}-acetic acid 2, 2-bis- ethylcarbarnoyl- 2-phenyl-ethyl ester, (pyrrolidine-1-carbOlyl) -trifluoromethyl- biphenyl-2-carbOlyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbanoyl- 2-phenyl-ethyl ester, (rethyl-propylcarbalOYl) -trifluoromethyl- biphenyl-2-carbOflyl)-amil]-phenyl)-acetic acid 2, 2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, (iethyl-propylcarbafoyl)- 4 -trifluoromethyl- bipheiy1-2-carbOfl)-flilo] -phenyll-acetic acid 3 ,3-bis- ethylcarbanoyl-3-Phel-PrOPYl ester, (3-hydroxy-4- -trifluoroniethyl-bipheflyl- 2 carbonyl) -amino] -phenyl)-acetic acid 2 ,2-bis- ethylcarbamoyl- 2-phenyl-ethyl ester, {3-methoxy-4- -trifluoroxnethyl-biphenyl-2- carbonyl) -amino) -phenyl}-acetic acid 2,2-bis- ethyJlcarbarnoyl- 2-phenyl-ethyl ester, (N (3-methoxy-4- -trifluoromethYl-biPhenYl> 2 carbonyl) -amino) -phenyll-acetic acid 2-pheflyl-2 ,2-bis- propylcarbafOYl-ethYl ester, 3-mnethoxy-4- -trifluoromethY1-biPhenY± 2 carbony1)-WlinfO]-Phnfl )-a&cetic acid 3,3-bis- ethylcarbamfoyl -3 -pheny- -propyl ester, 00 {(3-ethoxy-4- -trifluoromethYl-biPhenYl- 2 V')carbonyl) .amino]-phenYl}-acetiC acid 2,2-biS- o ~ethyi-carbaUoyl -2 -phenyl -ethyl ester, {3-ethoxy-4- -trifluororethYJlTiPhenY carbonyl) -amino] -phenyll-acetic acid 3, 3-bis- ethylcarbamofl-3Phefl-lProPYl ester, (3-isopropOXy- 4 -trifluoromethY1-bJiPhelI 2 carbonyl) -amino) -phenyll-acetic acid 2, 2-bis- ethylcarbamOyl2-Phelyl-ethYl ester, {3-isoprOpoxy- 4 -trifluoromethYl-biphelYl- 2- carbonyl) -aiino]-phefyll-aCetic acid 3. 3-bis- ethylcarbanlOyl3-Phelyl-Propyl ester, {3-proposy-4- -trifluorOmethYl-biPhefyl-l> carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbamfoYl>PhenYl-ethYl ester, {3-benzylOxy- 4 -trifluoromethylbiPhenYl>2 carbonyl) -amino] -phenyll-acetic acid 2,2-biS- ethylcarbafoyl- 2-phenyl-ethyl ester, {3-dimethylamiflo- 4 -trifluorOmflthyl-biPheflYl-2 carbonyl) -amino] -phenyl)-acetic acid 2, 2-bis- ethylcarbafoyl2phenYl-ethYl ester, (3-piperidifl-1-Yl- 4 -trifluoroJmethyl-biphefl- 2 carbonyl) -amino] -phenyll-acetic acid 2, 2-bis- 483 ethylcarbal-l2 -phenyl -ethyl ester, {3-pyrrolidif-1-Yl- 4 '-trifluorOmfethy1TiphenYl- 2 carbonyl) -amino] -phenyl)'-acetiC acid 2. 2-bis- en ethylcarbamfoYl- 2 -phenyl-ethYl ester, 4- -trifluoromethyl-biPheyl-l2-carbonyl) -wnino] benzoic acid S,3-bis-ethylcarbamfl-3-phenyl>ProPYI~ ester, 00 (2 2 -bis-ethYlCarbamfoYl2PhenYl-ethoxcycarbonyl- V)methyl) -trlfluoromfethyl-biphenyW2-carbolyl) o amino]-beflzoiC acid benzyl ester, 5-c 2bsehycraol2-hnlehoyabnl methyl) [(4'-tilooety~ihnl -abnl- amino] -benzoic acid, (2,2-i-tycramy -hnletoyabnl methyl) -trifluoromethyl-biphel-2-Carbolyl) amino] benzoic acid ethyl- ester, and (2,2-i-tycramy -hnletoyabnl methyl) loomty-ipey -c~bnl- axnino]-ber±ZOiC acid methyl ester. 28. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of' 2- (2-{3-methyl-4- -trjfluoromethyl-biphel- 2-carbonyl) -amino) -phenyl}-acetox-ymethyl) -2-phenyl-malolic acid diethyl ester, [methyl- -trifluorofl'ethYl-biphenfl- 2 -carbonyl) -amnino] -phenyl) -acetoxymnethyl) -2 -phenyl -malonic acid diethyl ester, 2-phenyl-2- -trjfluoromethyl-biphenyl- 484 (N 2-carbonyl) -amino] -phenyl}-acetoxynethyl) -rualonic acid C) diethyl ester, 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -ialonic acid 0 5 diisopropyl ester, 2-phenyl-2-(2-{4-[ (4'-trifluoromethyl-biPheflYl- 2-carbonyl) -amino] -phenyl.}-acetoxylnethYl) -malonic- acid dimethyl ester, o 2-cyclopentyl-2-(2-( 4 -trifluoromethy1-biPhel- 2-carbonyl) -amino] -phenyl)-acetoxylethyl) -malonic acid diethyl ester, 2-phenyl-2- -triiluororethyl-biPheflYl- 2-carbony.) -amino] -phenyl)-acetoxyfethYl) -malonic acid dicyclohexyl ester, 2-benzyl-2- 1(4' -trifluoromethyl-biPhelYl- 2-carbonyl) -amino] -phenyll-acetOxymfethyl) -ialonic acid diethyl ester, 2- (2-{2-inethyl-4- -trifluorornethyl-bipheflYl- 2-carbonyl) -amino] -phenyl)-acetoxymethyl) -2-phenyl-malonic acid diethyl ester, 2-cyclohexyl-2- -trifluoromethyl-biphenyl- 2-carbonyl) -ami~no] -phenyl)-acetoxymethyl) -malonic acid diethyl ester, 2-pheny1-2-(2-{2-trif1uoromfethy-4-(4'-trifluoro- methyl-biphenyl-2-CarbOnyl) -amino] -phenylj-acetoxymethyl) malonic. acid diethyl ester, 2-pyridin-2-yl-2-(2-{4-I(4'-trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenylj-acetoxylethYl) malonic acid diethyl ester, 485 biphenyl-2-carbOlYl) -amino] -phenyl)-acetOx-YmethYl) inaloni c acid diethyl ester, ci 2-phenyl-2-(2-(3-.trifluorOmethYl 4 (4'-triflnoro- methyl -biphenl-l2 caronyl) -amino] -phenyl) -ace toxyme thYl) nalonic acid diethyl ester, phenyl) -acetoxymethyl) -2 -phenyl-maloliC acid diethyl ester, phenyl)-acetOXymflthy1)-2-phelJmalOflic acid diethyl ester, 2-phenyl-2-(2-{ 4 (3'-trifluoromnethYl-biPhel-l2- carbonyl) -amino] -phenyl)l-acetoxylethYl) -malonic acid diethyl ester, 2- [isopropyl- (4 '-trifluoroznethyl-biPheflyl- 2 carbonyl) -amino] -phenyll-aCetOXYmfethYl) -2-phenyl-malolic acid diethyl ester, 2- (2-{4-[cyclOhexyl-(4' -triiluoromethyI-bipheny1-2- carbonyl) -amino] -phenyll-acetoxylethyl) -2-phenyl-malonic acid diethyl ester, 2-hnl2(-4[4-rfurmty-ihnl2 carbonyl) -amino] -phenyl)-acetoxyfethYl) -malonic acid dipropyl ester, 2-phenyl-2-(2-{ 4 -trifluoromethyl-biPhel-2- carbonyl) -amino] -phenyl)-acetoxymflthyl) -malonic acid diisobutyl ester, 2- [ethyl- -triflnoromethyl-biphenyll- 2 carboflyl) -amino] -phenyl)-acetoxyfethyl) -2-phenyl-maloli acid diethyl ester, 2- 3-ethyl-4- -trifluorometbyl-biphelyl-2 carbonyl) -amino] -phenyl)-actoxymlethyl) -2-phenyl-maOlic acid diethyl ester, 2- (2-{3-isopropyl- 4 -trifluoromethyJ-biPheflYl-2 carbonyl) -amino] -pheny1}-8CetOXYfllthYl) -2-pheny-faJliC o 5 acid diethyl ester, 2-2f-sbtl4('tifurmty-ihnl2 00 carbo'nyl) -amino] -phenyl I-acetoxymethyl) -2 -phenyl-malolic 0' acid diethyl ester, carboflyl) -amino] -pheny..-aCetOXymflthYl) -2-pheny1-ma1OliC acid diethyl ester, 2-(2-(3-bromo-4-[ -trifluoromethy1~biPhefYl-2 carbonyl) -amino] -phenyl) acetoxynlethyl) -2 -phenyl-malOflic acid diethyl ester, 2- (2-(3-dimethy1Carbamfl- 4 -trifluorOflethY1- biphenyl-2-CarbOlYl) -amino] -phenyJJ-aCetOXYmethY-) -2- phenyl-maloflic acid diethyl. ester, 2- (2-{3-diethyCarb1l- 4 -trifluorimethy- biphenyl- 2-carbony-) -amino] -phenyl) -acetoxynethyl) -2- phenyl-malo:liC acid diethyl ester, 2- (2-3-diisopropylcarbamoYl- 4 -tritluoromethyl- biphenyl- 2-carbonyl) -amino) -phenyl) -acetoxymethyl) -2- phenyl-maloflic acid diethyl ester, 2- (ethyl-methylcarbamoYl) -trifluoro- methy1-biphel-2-CarbOflYl) -amino] -pheny1)-aCetOXYtfethYl) -2 -pheny-fa1Oflic acid diethyl ester, 3- (ethy1-methyCarbaTOYl) -trifluoromethyl- biphenyl-2-CarbOlYl) -amino] -phenyll-acetic acid 2, 2-bis- ethylcarbaloyl-2-phenyl-ethyl ester, (pyrrolidine-1-CarbOlYl) -4-11(4' -trifluoromethyl- (1)bipheflyl-2-CatbOflYl) -amino] -phenyl)-acetiC acid 2. 2-bis- en ethylcarbafOYl- 2-phenyl-ethyl ester, o 5 trifluoromethYl-biPhefylY2-carbonYl) -amino] -phenyl) acetoxymethyl)-malOfliC acid diethyl ester, 0 trifluoromethYl-biPheflY12-CarbonYl) -amino] -phenyl) o acetoxymethyl)-malOliC acid diethyl ester, 2-{3-dimethylcarbafoYl-4- -trifluoromnethyl- biphenyl-2-carbOlYl) -amino] -phenyili-acetoxy) -ethyl] -2- phenyl-malonic acid diethyl ester, 3-diinethylcarbamOyl-4 E -fluoro- biphenyl-2-CarbOl)-amino] -phenyl)-acetOxYlfethyl)-2- phenyl-ralOflic acid diethyl ester, 2-2(-[('boobpeyl2-abnl-mLo1)3 dimethylcarbamfOYl-Phnfll-acetoxyinethyl) -2 -phenyl-inaloflic acid diethyl ester, 2-(2-(3-dimnethylcarbamOYl-4- -trifluoroinethyl- b-iphenyl-2-CarbOlYl) -amino] -phenyl)-acetoxylfethYl) -2- phenyl-maloflic acid dimethyl ester, 2-cyclopenty1-2-(2-{3-diffethylcabamoyl> 4 4 trifluoromethyl-biPhnYl2carbOnYl) -amino] -phenyl)- acetoxyznethyl)-malolic acid diethyl ester. 2-cyclohexy1-2- dnethyl carbamoyl 4 4 trifluorornethyl-biPhenYl 2 -carbonyl) -amino] -phenyl) -acetoxyniethy1)-maloliC acid diethyl ester, 2-2(-('clr-ihny--abnl-mn]3 dimethylcarbamfoyl-pheflYl) -acetoxymethyl) -2-phenyl-malonic 488 acid diethyl ester, en dimethylcarbafoYl-PhenYll -acetoxymethyl) -2-phelyl-mfaloflic 00 acid diethyl ester. dimethylcbanllOcalbhefl -amto]pey-ctymethyl) -2 ~hnlmlfi -hnllncacid diethyl ester, 0- 2 2 3 -dimethylcarbmylO4 (methyl4-trif luoro- ci methyl-biphenfl'l2-CarbonYl) -amino] -phenyl-acetoxynethyl) -2 phenyl-maOliC acid diethyl ester, 2-[3(22-3dimethYlCarbalOYl 4 [(ehy'-trifluoorohy- 15mehyl-2bipheflylCbn))-amino]n phaey-ceoYfltl) 2-phenyl-malolic acid diethyl ester,- 2 2 3 dimethlclrarbamoY-1(4trifx oromth lomthbiphenyl-2-Caball)-mio bohny)-aetoXY)-propyll aeoyty)2-phenyl-maloflic acid diethyl ester, 2 -(2-{3-dimehlrba4'triloY1 ometho2W 4 -ny-2 trfnluoromth-lbieylcarboYl-m]-phenyl acetoxymethYl-2-phenyl-malonic acid diethyl ester, (5-chlr-4'mtrilu4-rO6-ethyl-i-theflu- 2 carbonyl) -amino] -3cdimethylcarbamOYPhenYl -2-phenyl-falOflic acid diethyl ester, 2- (2-{3-dimethylCarbamloyl- 4 -trifluoroflethYl- biphenyl-2-carbolyl) -amino] -phenyl)-acetoxymethyl) -2- phenyl-malolic acid 2,2, 2-trifluoroethyl ester. 2 -(2-(3-dimfethylcarbamoyl-4(2fluoro- 4 trifluorOmethYlbiphenYl-2-carbonyl) -amino] -phenyll acetoxymethylhz2PhenYl-malonic acid diethyl- ester. m 2 2 -(5-dimethy1carbafl-2-f1uoro- 4 trifluoromethYl-biPhenYl- 2 -carbonyl) -amino] -pheflyl) o 5 acetoxymethY1-2-phenYlmalon~ic acid diethyl ester, 00 trifluoromethyl-biphenyl- 2 -carbonyl) -amino] -phenyl) o acetoxymethYl)2-PhenYl-malonic acid diethyl ester, trifluoroflethYlbiphenYl±2-carbonYl) -ami-no] -phenyl) acetoxymethYlb-2phel-malolic acid diethyl ester, 2-(2-{3-dimethY1CarbamOYl- 4 -fluoro-4' trifluoromethyl-biphefl-2-carbonYl) -amino] -phenyl) acetoxymetbyl) -2 -phenyl-mlalofliC acid diethyl ester, 2 2 4 3 I-ch1oro4'trifluoromethyl-biphenll 2 carbony-) -amnino] -3-dimethy1CarbIiOY1-PhenYl)h acetoxymethyl)2-PheflYl-malonic acid diethyl ester, direthylcarbamolOl-4- trifluoromethyl biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetoxymTethYl) nitro -pyridin-2 -Y1)-malonic. acid diethyl ester, s-amino-pyridil-2-Yl) (2-(3-dimethYloarbalOYl- -trifluoromethYl-biPhefl-2-carbonYl) -amino] phenyl) -acetoxymethyl) -malonic acid diethyl ester, 2-{3-dimethY1CarbaWoyl"--[(4' -trifluorornethyl- biphenyl-2-CarbOfYl) -amino] -pheny1}-acetoxymlethYl pyridii-2Y-lalOnic acid diethyl ester, 2-( 2 3 chloro-5-dimethylca2CbamoylO-2fluoro- 4 4 trifluorOmethYl-biPhenYl-2-carbonYl) -amino] -phenyl)- acetoxymethyl)v>phenYl-malonic acid diethyl ester, 2 2 -(3-bromo-5-dimethY1carbawoYl2-fluoro- 4 trifluoromethy--biphel-2-carbonyl) -amino] -phenyl) en acetoxymethyl -phenyl-malOlic acid diethyl ester, 2- (2-(3-dimethyJ-CarbamOYl- 4 -trifluoromfethyl> o 5 biphenyl-2-CarbOflyl) -amino] -pheny1}-aCetOXymethYl) 2 tolyl-malonic acid diethyl ester, 00 '4 2- (2-(3-dimethY1CarbamOYl> 4 -trifluoromfethY1- 0 ~biphenyl-2-CarbOl)-amino] -pheny1)-aCetOXYmethYl> 2 -in- 0 tolyl-malofliC acid diethyl ester, 2- (2-{3-dinlethy1CarbafOYl- 4 -trifluorOmfethyl- biphenyl-2-CarbOlYl) -amino] -pheny1}-acetOXyiflthYl- 2 -p- tolyl-maloflic acid diethyl ester, 2-2clr-hnl--273dmtycraol4 -trifluoromethY1-biPhefylY2-CarbonYl) -amino] -phenyl'- acetoxymethYl)lflalOflic acid diethyl'ester, 2- (3-chioro-phelyl) (2-{3-dimethycarbamfOYl- 4- (4'-tilooety-ihnl -abnl-amino] -phenyl)- acetox-ymlethylhlflalOniC acid diethyl ester, 4-chioro-pheny))-2- (2-{3-dimethycarbamfoyl- 4 -trifluorOmethY1-biPhefl2-carbonYl) -amino] -phenyl)- acetoxynethylviflaloflic acid diethyl- ester, 2- (3 -dimethylca~rbamOY1- 4- -trifluoroflethy1- biphenyl-2-carbolYl) -amino] -pheny11-acetoxyflethYlV>2 phenyl-Succilic acid diethyl ester, 2-f 3-dimethylcarbamfoyl- 4 -trifluoromethyl- biphenyl-2-carbol) -amino] -phenyl)-acetoxyfethYl 2- inethoxy-pheflyl)inalOflic acid diethyl. ester, 2-C 2-(3-diinethylcarbauOy1- 4 -trifluoromfethyl- biphenyl-2-carbOnYl) -amino] -pheny1}-acetOXYmfethYl (3- methoxy-pheny1)-malonic acid diethyl ester. 2- (2-{3-dimethy1CarbW1OYl- 4 -trifiuoromfethy1- en bipbenyl-2-CarbOlYl) -amino]-phefl)-8CetoxCynethYl)> methoxy-phel)-malOfliC acid diethyl ester, o 5 2 2 4 [(,4'bistrifuoromethY-biphenyl- 2 carbonyl) -amino) -3 -dimethy1Carbamll-Phel) acetoxymethYlv2-PhenYl-malonic acid diethyl ester. 0 ~carbonyl) -amino] -3 -dizethylcarbWmolOY-PheflYl)- acetosymnethyl )-2-phenyl-malOflic acid diethyl ester. 2- (2-{3-dimethyJlOarbamol- 4 -[(6-fluoro-4' trifluoromethYlmbiPhefl> 2 -carbonyl) -amino] -phenyl acetozymethYJ)2PhenYl-malonic acid diethyl ester. 2 -[2-(2-{3-dimethY1CarbamOYl4[ (5-methyl-4 trifluoromethYl-biphenYl-2carbonyl) -amino] -phenyl)- acetoxy)-ethylh2-Phel-lmalonic acid diethyl ester, z-(2-{3-dimethyCarbamoy- 4 (5-ethoxy-4'- trifluoromethYl-biPhel-2-carbonyl) -amino] -phenyl) acetoxymethyl)-2-Phefl-malonic acid diethyl ester. 2-(2-{3-dimethYlcarbamfl- 4 (5-isopropoxy-4'- trifluoromethYl-biPhenyl' 2-carbbflyl) -amino] -phenyl) acetoxymethyl-2-PhenYl-malonic acid diethyl ester, 2-2(-4(,'bstifurmty-ihnl2 carbonyl) -amino] -3 -dimethy1Carbamfl-Phenfl)I-acetoxy) ethy1)-2-phelmfalofic acid diethyl ester, 2 -{3-dimethy1CarbamOYl-4-( 6 -methoxct 4 F-trifluoro- methy1-bipheny1-2-crbOl)-amino] -phenyl}-acetoxYlfethylV- 2-phenyl-nalorlic acid diethyl ester, 2- 2{3-dimethY1CarbamolY 4 (3-methyl-4 -trifluoro- methy1-bipheny1-2-carbonYl) -amino] -pheny11-aCetOXYmlethYl)- 2-phenyl-falOflic acid diethyl ester, en (2 ,4-bis-trif1UOrOffethYl-beflzoYlamino) -3- dimethylcarbaDOY1-Phenfll -acetoxymethy1-2-Phnfl-lmalonic o 5 acid diethyl ester, 2- 2(3-dimethy1Carba1OY1- 4 -methy1-biphenfl- 2 00 carbonyl) -amino) phenyl) -aCetOXYrfethY1V>2 -phnyl malonic o acid diethyl ester, o 2 2 3 diethylcrbamoy-4(2ethyl- 4 trifluoro- methy-belZOyaminO) -phenyl] -acetoxyiethy1-2-PhenYl- maloflic. acid diethyl- ester, 2- (2-{3-dimethY1carbamolY 4 -ethyl-bi'pheflyl- 2 carbonyl) -amino] -phenyl) -acetoxymethyl-)-2 -phenyl-malolic acid diethyl ester, 2- (2-(3-di-nethylcarbamoY1- 4 -isopropenyl- biphenyl- 2-carbonyl) -amino) -phenyl )-acetox-yrethyl phenyl-malolic acid diethyl ester, (2-{3-dimethylcarbarfl- 4 -isopropyl- biphenyl- 2-carbony-) -amino] -phenyl) -acetoxymethy1-2-Phnfl-lmalonic acid diethyl ester, 2- (2-{3-dilethYlcarbamlOYl- 4 -trifluoromfethyl- biphenyl- 2-carbonyl) -amino f-phenyl} -acetoxymethyl thiophen-2-Y1-floflic acid diethyl ester, 2- (2-{3-dimethylcarbafoyl-4-[(4' -trifluoromethYl- biphenyl-2-CarbOlYl) -amino] -pheny1)-aCetoxymfethYl)- 2 thiophe±-3-Y1-maOflic acid diethyl ester, 2- (2-t4-dimethylcarbamolO-l5- -trifluorOflethyl- biphenyl-2-CarbolYl) -amino] -pyridin-2-yl) -acetoxyiethylV- 2-phenyl-mafliC acid diethyl ester, 2- (2-{3difl1thy1CarbamOYl- 4 -trifluoromethYl- 5biphenyl-2 -carbolyl) -amino] I phenyl) -acetoxymethyl (3 metby1-thiophefl>Y1>.-malonic acid diethyl ester, 2 (3dimethy1Carbam0Yl- 4 (4 F- trif luoromethyl- o biphenyl-2-CarbolYl) -amino] -pheny11-acetoxymelthyl 00 mthy1thilh2flYlmalonic acid diethyl ester, 2 f3-dfethY1Carb- x L (4'f lu mtrifuoromphey- o bhnyl-2-arbnOflphl) -ano] ypheny1)-etOXym~hlV>lo tiz12ymaOiCacid diethyl ester, carbonyl) -amino) pheny1) -aCetOXYflethY1V>2 PhenYl-malonic diethyl ester, 2carbonyl) -amino pheny-actoxymethY1-2-PhenYlmalonic diethyl ester, 2- (2-13-iSOnrOOXr4-(4' -trifluoromelthYlbiPhenYl>2 -amino]-pheny1}-aCetoxymethYlh2.PlhenYlmalonic acid diethyl- ester, 2-(2-{3-beyOXY4-[ (4'trifuoromthy-biPhfYl-- carbonyl) -amino] -pheny1)-aCetoxyDthYl )-2-pheny-fatOfliC acid diethyl ester, 22 2-pe--ydor-43-pieii 'ti~ormtY-bihfll-> carboyl-mino] 2cphenyF amtoX -pethY1V>PheoYmloni maloniC acid diethyl ester, methy1-biphenfly2-carbonYl) -amino] -pheny1}-aCetoxymfethYl)h 494 u malonic acid diethyl ester, 2- (2-.{3-dimethylaifo-4-[(4' -trifluoromethYl- m biphenyl-2-CarbOlYl) -amino] -pheny1}-aCetOXYflethYlV>2 phenyl-maloflic acid diethyl ester, biphenyl-2-carbOlYl) -amino] -pheny1-acetOXYmethYlW- 2 00 phenyl-inaloflic acid diethyl ester, o 2-(2-(3-diethYlamilO-4-[(4'-trifluorometbYl- 0 biphenyl-2-CarbOlyl) -amino] -pheny1)-acetOXYmfethYlh>2 phenyl-malofliC acid diethyl ester. 2-2(-hoo4[4-rfurmty-ihnl2 carbonyl) -amino] -benzoy2loxy1-ethYl) -2-phelyl-mlaloflic acid diethyl ester. {3 -ethoxycarbonyl- 4 -trifluorolmethyl- biphenyl-2-CarbOlYl) -amino) -phenyl}-acetoxlflfethYl)- 2 phenyl-maloflic acid diethyl-. ester, 2- (3-{3-dimethylcarbamOYl- 4 -trifluoromethyl- biphenyl- 2-carbony-) -amino] -phenyli -propionyloxcymethyl) -2-pheny1-ma-Oflic acid diethyl ester,: 2-(2-t3-benflxyXCarbOfl4- -trifluorornethyl- biphenyl-2-CarbolYl) -amino) -pheny1)-aCtOXYmfethYl) -2- phenyl-malolic acid diethyl ester, 2-2{-abx--('tifurmty-ihnl2 carbonyl) -amino] -pheny1}-aCetOXYmfethY-)-2-phenyl-naloflic acid diethyl ester, 2-{3-isopropoxycarbol-4- -trifluorornethyl- biphenyl-2-CarbolYl) -amino I-phenyl) -acetoxymethyl) -2- phenyl-maloflic acid diethyl ester, 2- (2-{3-methOSycarbOfl-l 4 -trif3-uoromethyl- 495 biphenyl-2-CdrbOlYl) -amino] -pheny)-acetoxymethyl) -2- phenyl-malOflic acid diethyl ester, 2- (2-(3-acetylamilO- 4 -trifluoromethY1-biPhelL 2-carbonyl) -amino] -phenyl1}-aCetOXYmfethYl) -2-phenyl-flalOfliC o 5 acid diethyl ester, 2- (2-{3-methoxycarbonylamin0- 4 -trifluoromfethyl- 00 ci biphenyl-2-CarbOflYl) -amino] -phenyl) -acetoxymethyl) -2- o phenyl-malOflic acid diethyl ester, methyl-bipheflYl-2-CarbonYl) -amino] -pheny1}-acetOXYmetbYl) -2-pheny1-maloliC acid diethyl ester, 2-phenyl-2-(2-{ 6 (4'-trifluOrOmfltby1-biPheflYl- 2 carbonyl) -amino] -bipheny1-3-y1)-actOXYI1ethYl) -malonic acid diethyl ester, 2-(2-(3-fOrfyll -trifluoromethY1-biPhel-l 2 carbonyl) -amino] -pheny1)--acetoxymfethYl) -2-phenyl-laIOfliC acid diethyl ester, 2- (2-{3-dimetlyamTiflomethYl- 4 -trifluoroiflthy1- biphenyl-2-CarbOlYl) -amino] -pheny1)-aetOXYflethYl) -2- phenyl-malonic acid diethyl ester, 2 -(2-{3-(methO2Cy-methYlcarbamoyl)- 4 -[(4'-trifluoro- methyJ.-biphefl-2-CarbolYl) -amino] -pheny1}-aCetOXYmhethYl) 2-phenyl-malolic acid diethyl ester, 2- (2-{3-isobutyryl-4-[(4' -trifJluoromfety-biPhefylY carbonyl) -amino) -pheny1)-aCetOXYmethYl) phenyl-rnalofliC acid diethyl ester, and 2-C 1hydroxy-2-methY1-PrOPYl) trifluoromethy1-biPhefl-2carbonYl) -amino] -phenyl)- acetoxyinethyl) -2-phenyl-malonic acid diethyl ester. 496 29. The ester compound or a prodrug thereof, or a Mn pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of o 5 4 U-trifluoromethyl-biphenYl-2-carboxTlic acid 4-[2- phenyl-2,2-bis- (2,2,2-trifluoro-8thylcarbamoyl) 00 ethoxycarbolyilethyi] -phenyl ester, 0) biphenyl-2-carbOXYlic acid 4- [2-phenyl-2 ,2-bis- 0 ~(2,2,2-~trifluoro-ethylcarbamfOYl) -ethoxycarbolIfethYl- phenyl ester, 4' -trifluoromfethylbiPhenyl- 2-carboxyl-ic acid 4-(2,2- bis -ethylcarbafoyl- 2 phenyl-ethoxycarbolmethYl) -phenyl ester. 4, -trifluoromethYl-biphenY1>2carboxcylic acid 4- (2,2- bis -ethylcarbamfOYl- 2 phenyl-ethoxycarbolm1thYl) -2- chioro-phenyl ester, 4' -trifluoromethYl-biphefl-l-carboxcylic acid 4- (3.3- bis -ethylcarbafoYl- 3 phenyl-propoxycarboflYlmethYl) -2- chloro-phelyl ester, 4 -trifluoromethyl-biphenyl-2carboxcYlic acid 4- (3,3- bis-ethylcarbamoyl-3-pheflProPoxWcarbonYl) -phenyl ester, and 4' -trifluoromethyl-biPhefylY1>carboxWlic acid 4- (3,3- bis-ethylcarbalY13PhenYl-proPoxWcarbonyl) 6-dichioro- phenyl ester. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of carbonyloxy) -phenyl] -acetoxymethyll -malonic acid diethyl Mn ester; [3-dimethylcarbamlfY 4 -trifluoromethyl- o 5 biphenyl-2-CarbOllOXY) -phenyll -acetoxymethyl)-2-Phefl- malonic acid diethyl ester, 00 2-2- [3-methoxy-4- -trifluorornethYl-biPhefYl-2 o carbonyloxy) -phenyl] -acetoxyniethyl) -2 -phenyl malonic acid 0 diethyl ester, and 4-1 (4 -trifluoromethyl-biPhefl2-carbonYl) -amino II- benzoic acid 3- 2-trifluorO-ethyCarbamOYl) naphthalefl-1-Yl] -propyl ester. 31. The ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to claim 1, which is selected from the group consisting of 2- (2-{3-dimethylCarbamfoyl- 4 -trifluoroniethyl- biphenyl-2-CarbOnYl) -amino] -phenyl)-acetox-YflethYl) -2- isopropyl-malonic acid diethyl ester, 2 -sec-butyl2(2(3-d3.ethYlcarbamoYl 4 4 trifluoromethyl-biPhefl-2-carbonYl) -amino] -phenyl)- acetoxymethyl)-2-malonic acid diethyl ester, 2-(2-{3-dimethylCarbamoyl- 4 -trifluoromethyl- biphenyl-2-carbonyl) -amino] -pheny1}-aCetOXYHmethYl) -2- isobutyl-fa-oflic acid diethyl ester, 2-(2-(3-dimethylcarbamofl- 4 -trifluoromlethyl- biphenyl-2-carbOnyl) -amino] -phenyl1-8CetoxymethYl) -2- propyl-malonic acid diethyl ester, 2-{3-dimethylcarbamoYl- 4 -trifluoromethyl- 498 ci biphenyl-2-carbonyl)-amino] -phenyl) -acetowymethyl)-2-ethyl- malonic acid diethyl ester 2-butyl-2-(2-{3-dimethylcarbamayl-4-[(4'- trifluoromethyl-biphenyl-2-carbonyl) -amino] -phenyl) acetoxymethyl)- malonic acid diethyl ester, 2-allyl-2-(2-{3-dimethylcarbamoyl-4-[( 4 C trifluoromethybiphenyl-2-carbonyl) -amino] -phenyl)- .acetoxymethyl) -malonic acid diethyl ester, o 2-(2 (3-imethylcarbamoyl-4-[(4'- trifluoromethyl- biphenyl-2-carbonyl)-amino]-phenyl)-acetoxy)-2,2-bis- ethoxycarbonyl-propionic acid ethyl ester, and 2- (2-{3-dimethylcarbanoyl-4- (4'-trifluoromethyl- biphenyl-2-Carbonyl)-amino]-phenyl}-acetoymethyl)-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 one of claims 1 to 31 and a pharmaceutically acceptable carrier. 33. An MTP (microsomal triglyceride transfer protein) inhibitor. which comprises the ester compound or a proardg thereof, or a pharmaceutically acceptable salt of either according to any one of claims 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 one of claims 1 to 31 as an active ihgredient. 499 35. An agent for -the treatment or prophylais of arteriosclerosis, which. comprises the ester compound or a C prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims 1 to 31 as an active O .5 ingredient. 00 S36. An agent for the treatment or prophylaxis of coronary artery o diseases, which comprises the ester compound or a prodrug C thereof, or a pharmaceutically acceptable salt of either according to any one of claims 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 one of claims 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 one of claims I 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 one of claims 1 to 31 as an active ingredient. An agent for the treatment or prophylaxis of hyperlipidemia. arteriosclerosis, coronary artery diseases, obesity, diabetes or hypertension.. which comprises MTP inhibitor selectively 500' 0 inhibiting MTP (microsomal triglyceride transfer protein) in C- the small intestine and a pharmaceutically acceptable carrier. M 41. The agent for the treatment or prophylaxis according to claim 40, wherein the MTP.inhibitor does not substantially o .inhibit MTP in the liver but substantially inhibits only .MTP CO in the small intestine. 00 o 42. The agent for the treatment or prophylaxis according to C 10 claim 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 a according to claim 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 any one of claims 40 to 43, wherein the MTP inhibitor is a compound having at least one ester bond. The agent for the treatment or prophylaxis according to claim 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 C( substance. U C, 46. The agent for the-treatment or prophylaxis according to any C one of claims 40 to 45, wherein the MTP inhibitor is the ester compound or a prodrug thereof, or a pharmaceutically acceptable in salt of either mentioned in any one of claims 1 to 31. 00 In 47. A method for the treatment or prophylaxis of hyperlipidemia, 0 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 claim47, .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 claim 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 or more of the normal level. 50. The method according to any one of claims 47 to 49, wherein the. compound has at least one ester bond. 51. The method according to claim 50, wherein after the compound having at least one ester bond exerts MTP inhibitory activity, the* 502 0 ester moiety of the compound is metabolized in blood to become 1) an inactive substance. 52. The method according to any one of claims 47 to 51, wherein the compound -is the ester compound or a prodrug thereof, or a V pharmaceutically acceptable salt of either mentioned in any one 00 of claims 1 to 31. cn 0 53. The agent for the treatment or prophylaxis-accordirg to any one of claims 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 claim 53, wherein other antibyperlipidemic drug is a Sstatin-type drug. The-agent for the treatment or prophylaxis according to claim 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 any one of claims 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 claim 56, wherein other anti-obesity drug is mazindol or/and orlistat. Cn 58. The agent' for the treatment or prophylaxis .according to any one of claims 40 to 46, wherein the agent is an agent O 5 for the treatment or prophylaxis of diabetes which is used in combination with other anti-diabetic drug(s). 00 o 59. The agent for the treatment or prophylaxis according to 0 claim. 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 claim 58, wherein other anti-diabetic drug is one or -more drug(s) selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohbexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, boglibose, acarbose and pioglitazone hydrochloride. 61. The agent for the treatment or prophylaxis according to any one of claims 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 claim 61, wherein other anti-hypertension drug is one or more 0 drug(s) selected from the group consisting of loop diuretics, angiotensin converting enzyme inhibitors, angiotensin II Cn receptor antagonists, calcium antagonists, P-blockers, a,p-blockers and a-blockers. o C 63. The agent for the treatment or prophylaxis according to 00 Sclaim 61, wherein other anti-hypertension drug is one or more V drug(s) selected from the group consisting of furosemide o 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 .505 0 0 C( hydrochloride, bopindolol malonate, bevantolol hydrochloride, o labetalol hydrochloride, arotinolol hydrochloride, amosulalol M hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazocin hydrochaoride, O 5 bunazocin hydrochloride -delayed release, urapidiil and C -phentolamine mesylate. 00 64. Use-of the agent for the treatment or prophylaxis according o to any one of claims 40 to 46 and other antihyperlipidemic drug(s) for the treatment or prophylaxis of hyperlipidemia. The. use according to claim 64, wherein other antihyperlipidemic drug is a statin-type drug. 66. The use according to claim 65, 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 any one of claims 40 to 46 and other anti- obesity drug(s) for the treatment or prophylaxis of obesity. 68. The use according to claim 67;.wherein other anti-obesity drug is mazindol or/and orlistat. 69. Use of the -agent for the treatment or prophylaxis according to any one of claims 40 to 46 and other anti- diabetic drug(s) for the treatment or prophylaxis of diabetes. 506 0 0 .70. The use according to claim.69, wherein other anti-diabetic drugs are one or more drug selected from the group consisting Nq of insulin preparations, sulf onylurea drugs, insulin secretagogues, sulfonamide drugs, biguanide drugs, 0 c a-glucosidase inhibitors and insulin resistance improving O 00 drugs. In S71. The use according to claim 69, 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 72. Use of the agent for the treatment or prophylaxis according to any one of claims 40 to 46 and other anti-hypertension. drug(s) for the treatment or prophylaxis of hypertension. 73. The use according to claim 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 claim 72, wherein other anti-hypertension drug is one or more drug(s) selected from the ci C group consisting of furosemide delayed release, captopril. Qcaptopril delayed release, enalapril maleate, alacepril, M delapril hydrochloride, silazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride. quinapril hydrochloride. trandolapril. o perindopril erbumine, losartan potassium, candesartan Scilexetil, nicardipine hydrochloride, nicardipine o hydrochloride delayed release, nilvadipine, nifedipine, C 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, 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. A pharmaceutical composition comprising an effective amount 508 0 c of the ester compound-or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any one Sof claims 1 to 31, a pharmaceutically acceptable, appropriate Ce CN amount of ethanol and pr6pylene glycol fatty acid ester. CA 76. The pharmaceutical composition according to claim 75, which 00 -comprises 25 to 35% by weight of ethanol and 65 to 75% by weight t n of propylene glycol fatty acid ester, 77. A capsule formulation comprising the pharmaceutical composition according to claim 75 or claim 76. 78. The capsule formulation according to claim 77, wherein the capsule formulation is a hard capsule or soft capsule. 79. A biphenyl compound represented by the formula (100) R2"' 4' 0 (CH) 0' 3 Rl' wherein R 1 is hydrogen, CL-C alkyl, halogen, halo CI-Cs alkyl or Ci-C6 alkoxy; R 2 is hydrogen, Ci-C 6 alkyl, halogen, halo Ci-C6 alkyl or C 2 -C 6 alkenyl; R 3 is -CON (R 1 1 a)(R 12 a) wherein R 11 a and R 12 z are each i independently hydrogen, Ci-C 6 alkyl, optionally substituted fC 6 -C 14 aryl. optionally substituted C 7 -C 16 aralkyl, CI-C 6 alkoxy, M or R 11 a and R 12 a may be taken together with the nitrogen to which ci they are attached to form S-N )P 00 i ci o (in which p is an integer of 0 to 2); R 4 is hydrogen, halogen, Ci-C 6 alkyl or halo CI-C 6 alkyl; R 50 is hydrogen, CI-C 6 alkyl, optionally substituted C 6 -C 14 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. The biphenyl compound according to claim 79, wherein R' is hydrogen, R 2 is halo Ci-C 6 alkyl, R 3 is -CON(Rllb)(R1 2 b) wherein R 11 b and R 12 b are each independently hydrogen or Ci-C 6 alkyl, or R 11 b and R 12 b may be taken together with the nitrogen to which they are attached to form -No )Qp (in which p is an integer of 0 to 2), R 4 is hydrogen, and R 50 is hydrogen or CI-C 6 alkyl, or a prodrug thereof, or a pharmaceutically acceptable salt of 510 in 0 either. ci U C)l 1B. The use of the ester compound or a prodrug thereof, or a n pharmaceutically acceptable salt of either according to any one of claims 1 to 31 for the preparation of a medicament for the Streatment or prophylaxis of hyperlipidemia. in 00 82. The use of the ester compound or a prodrug thereof, or a. CN I pharmaceutically acceptable salt of either according to any one S 10 of claims 1 to 31 for the preparation of a medicament for the c "treatment.or prophylaxis of arteriosclerosis. 83. The use of the ester compound or a.prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims I to 31 for the preparation of a medicament for the treatment or prophylaxis of'coronary artery diseases. 84. The use of the ester compound or a'prodrug thereof, or a pharmaceutically acceptable salt of either according to any-one of claims 1 to 31 for the preparation of a medicament for the treatment or prophylaxis of obesity. use of the ester compound or a prodrug thereof,.or a pharmaceutically acceptable salt of either according to any one of claims 1 to 31 for the preparation of a medicament for the treatment or prophylaxis of diabetes. 86. The use of the ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either according to any one of claims 1 to 31 for the preparation of a medicament for the treatment or prophylaxis of hypertension. 8.7. The use of MTP inhibitor which selectively inhibits MTP. in O the small intestine for the preparation of a medicament for the Streatment or prophylaxis of hyperlipidemia, arteriosclerosis, en coronary artery diseases, obesity, diabetes or hypertension. 88. The use according to claim 87, wherein the MTP-inhibitor n does not substantially inhibit MTP in the liver but 00 substantially inhibits only MTP in the small intestine. In o 10 89. The use according to claim 88, wherein after the 0 c 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. The use according to claim 89, 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. 91. The use according to any one of claims 87'to 90, wherein the MTP inhibitor is a compound having at least one ester bond. 92. The use according to claim 91, 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. 93. The use according to any one of claims 87 to 92, wherein the MTP inhibitor is the ester compound or a prodrug thereof, or a pharmaceutically acceptable salt of either mentioned in any one of claims 1 to 31. 512 S94. An ester compound or a prodrug thereof, or a C pharmaceutically acceptable salt of either according to Sclaim 1, substantially as herein described with reference to C, any one of the Examples. A pharmaceutical composition according to claim 32 or in substantially as herein described with reference to C 00 Formulation I or Formulation II. ci in i 96. A method according to claim 47 substantially as herein described with reference to any one of the Test Examples. 97. The biphenyl compound according to claim 79, substantially as herein described with reference to any one of the Examples. Dated this 23rd day of December 2005 JAPAN TOBACCO INC. By its Patent Attorneys GRIFFITH HACK