Isoxazole and thiazole compounds and use thereof as medicine

• US 6,964,975 B2
• Filed: 02/19/2001
• Issued: 11/15/2005
• Est. Priority Date: 02/18/2000
• Status: Expired due to Fees

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kirin Beer Kabushiki Kaisha
• Inventors: Ohta, Hideo, Yagi, Mikio, Watanabe, Tomoko, Nagao, Rika, Ueno, Akihiro
• Primary Examiner(s): STOCKTON, LAURA LYNNE
• Application Number:
  US10/204,173
• Publication Number:
  US 20030114505A1
• Time in Patent Office: 1,730 Days
• Field of Search: 548/214, 548/245, 514/380, 514/372
• US Class Current: 514/372
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 261/14 Nitrogen atoms
• CPC Class Codes: C07D 275/03 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to novel isoxazole and thiazole compounds having an excellent lysophosphatidic acid (LPA) receptor antagonistic activity represented by general formula [1] or salts thereof:
wherein R1 and R2 represents an optionally substituted alkyl group or the like; R3 represents a hydrogen atom or the like; R4 represent a group selected from the group consisting of (I) optionally substituted phenyl, aryl, or heterocycle, (II) substituted or nonsubstituted alkyl, and (III) substituted or nonsubstituted alkenyl, alternatively, R3 and R4 may form a ring structure together with a carbon atom to which they bind; and X represents an oxygen atom or a sulfur atom, provided that, when R3 is a hydrogen atom, R4 represents a group other than methyl, and the use thereof as a medicine.

Claims

1. A compound represented by general formula [1] or salt thereof:

wherein

R1 is a halogen atom or lower alkyl optionally substituted by one or more substituents independently selected from;

(I) alkyloxy, (II) alkylthio, (III) alkylamino, (IV) cyano, (V) nitro, (VI) cyclic amino, and (VII) a halogen atom; and

R2 is an optionally substituted aryl or aromatic heterocycle;

R3 represents a hydrogen atom, lower alkyl, or alkyl halide;

R4 represents a group selected from (I) optionally substituted phenyl, aryl, or heterocycle, (II) substituted or nonsubstituted alkyl, and (III) substituted or nonsubstituted alkenyl,

alternatively, R3 and R4 may form a five- to ten-membered cyclic structure together with a carbon atom to which they bind; and

X represents an oxygen atom or a sulfur atom,

provided that, when R3 is a hydrogen atom, then R4 represents a group other than methyl.

3. The compound or salt thereof according to claim 1, wherein X is an oxygen atom.

4. The compound or salt thereof according to claim 1, wherein the compound is represented by general formula [2]:

wherein

R1, R3, and R4 are as defined in claim 2;

Y and Z are each independently a carbon atom or a nitrogen atom; and

R5, R6, R7, R8, and R9 are each independently a group selected from

(I) a hydrogen atom;

(II) a halogen atom;

(III) lower alkyl optionally substituted by one or more substituents independently selected from;

(1) hydroxy, (2) amino, (3) alkyloxy, (4) alkylthio, (5) alkylsulfinyl, (6) alkylsulfonyl, (7) monoalkylamino or dialkylamino, (8) acyloxy, (9) acylamino, (10) aryloxy, (11) arylthio, (12) arylsulfinyl, (13) arylsulfonyl, (14) arylamino, (15) alkylsulfonylamino or arylsulfonylamino, (16) alkylureide or arylureide, (17) alkyloxycarbonylamino or aryloxycarbonylamino, (18) alkylaminocarbonyloxy or arylaminocarbonyloxy, (19) cyano, (20) cyclic amino, and (21) a halogen atom;

(IV) optionally halogenated alkyloxy, (V) cycloalkyl, (VI) aryl, (VII) aryloxy, (VIII) acylamino, (IX) acyloxy, (X) hydroxy, (XI) nitro, (XII) cyano, (XIII) amino, (XIV) monoalkylamino or dialkylamino, (XV) arylamino, (XVI) alkylsulfonylamino or arylsulfonylamino, (XVII) alkylureide or arylureide, (XVIII) alkyloxycarbonylamino or aryloxycarbonylamino, (XIX) alkylaminocarbonyloxy or arylaminocarbonyloxy, (XX) alkyloxycarbonyl or aryloxycarbonyl, (XXI) acyl, (XXII) carboxyl, (XXIII) carbamoyl, (XXIV) monoalkylcarbamoyl or dialkylcarbamoyl, (XXV) cyclic amino, and (XXVI) alkylsulfonyl or arylsulfonyl,

provided that, when Y is a nitrogen atom, R6 is absent, and Z is a nitrogen atom, then R7 is absent.

5. The compound or salt thereof according to claim 1, wherein

R1 is methyl or ethyl;

R3 is a hydrogen atom, methyl, or trifluoromethyl;

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, cycloalkyl, aryl, aryloxy, acylamino, acyloxy, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, arylamino, alkylsulfonylamino, arylsulfonylamino, alkylureide, arylureide, alkyloxycarbonylamino, aryloxycarbonylamino, alkylaminocarbonyloxy, arylaminocarbonyloxy, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, cyclic amino, and alkylsulfonyl and arylsulfonyl;

R2 is a group represented by the following formula;

Y and Z are each a carbon atom; and

R5, R8, and R9 are each independently a group selected from

(I) a hydrogen atom;

(II) a halogen atom;

(III) lower alkyl optionally substituted by one or more substituents independently selected from;

(1) hydroxy, (2) amino, (3) alkyloxy, (4) alkylthio, (5) alkylsulfinyl, (6) alkylsulfonyl, (7) monoalkylamino or dialkylamino, (8) acyloxy, (9) acylamino, (10) aryloxy, (11) arylthio, (12) arylsulfinyl, (13) arylsulfonyl, (14) arylamino, (15) alkylsulfonylamino or arylsulfonylamino, (16) alkylureide or arylureide, (17) alkyloxycarbonylamino or aryloxycarbonylamino, (18) alkylaminocarbonyloxy or arylaminocarbonyloxy, (19) cyano, (20) cyclic amino, and (21) a halogen atom;

(IV) optionally halogenated alkyloxy, (V) cycloalkyl, (VI) aryl, (VII) aryloxy, (VIII) acylamino, (IX) acyloxy, (X) hydroxy, (XI) nitro, (XII) cyano, (XIII) amino, (XIV) monoalkylamino or dialkylamino, (XV) arylamino, (XVI) alkylsulfonylamino or arylsulfonylamino, (XVII) alkylureide or arylureide, (XVIII) alkyloxycarbonylamino or aryloxycarbonylamino, (XIX) alkylaminocarbonyloxy or arylaminocarbonyloxy, (XX) alkyloxycarbonyl or aryloxycarbonyl, (XXI) acyl, (XXII) carboxyl, (XXIII) carbamoyl, (XXIV) monoalkylcarbamoyl or dialkylcarbamoyl, (XXV) cyclic amino, and (XXVI) alkylsulfonyl or arylsulfonyl, and

R6 and R7 are each independently a hydrogen atom, a halogen atom, chloromethyl, hydroxymethoxy, cyano, trifluoromethoxy, a group represented by formula [3];

wherein

n is 0 to 5;

Q is an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl; and

R10 is a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino, dialkylamino, aryloxy, arylthio, cyano, nitro, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, acyl, aryl, cyclic amino, and heterocycle,

or a group represented by formula [4];

wherein

n and m are each 0 to 5; and

R11 and R12 are each independently a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino or dialkylamino, aryloxy, arylthio, hydroxy, cyano, nitro, carboxyl, alkyloxycarbonyl or aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl or dialkylcarbamoyl, acyl, aryl, cyclic amino, and heterocycle;

or R11 and R12 may together form a five- to nine-membered heterocycle containing, in addition to a nitrogen atom, 1 to 3 oxygen atoms or sulfur atoms.

8. The compound or salt thereof according to claim 4, wherein

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, acylamino, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, and cyclic amino.

9. The compound or salt thereof according to claim 4, wherein R4 is nonsubstituted phenyl, 2-chlorophenyl, 2-bromophenyl, or 2-fluorophenyl.

11. The compound or salt thereof according to claim 5, wherein

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, acylamino, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, and cyclic amino.

14. The compound or salt thereof according to claim 5, wherein R4 is nonsubstituted phenyl, 2-chlorophenyl, 2-bromophenyl, or 2-fluorophenyl.

17. The compound or salt thereof according to claim 1, wherein

R1 is methyl or ethyl;

R3 is a hydrogen atom, methyl, or trifluoromethyl;

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, cycloalkyl, aryl, aryloxy, acylamino, acyloxy, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, arylamino, alkylsulfonylamino, arylsulfonylamino, alkylureide, arylureide, alkyloxycarbonylamino, aryloxycarbonylamino, alkylaminocarbonyloxy, arylaminocarbonyloxy, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, cyclic amino, alkylsulfonyl and arylsulfonyl;

R2 is a group represented by the following formula;

Y and Z are each a carbon atom;

R5, R8, and R9 are each independently a group selected from

(I) a hydrogen atom;

(II) a halogen atom;

(III) lower alkyl optionally substituted by one or more substituents independently selected from;

(1) hydroxy, (2) amino, (3) alkyloxy, (4) alkylthio, (5) alkylsulfinyl, (6) alkylsulfonyl, (7) monoalkylamino or dialkylamino, (8) acyloxy, (9) acylamino, (10) aryloxy, (11) arylthio, (12) arylsulfinyl, (13) arylsulfonyl, (14) arylamino, (15) alkylsulfonylamino or arylsulfonylamino, (16) alkylureide or arylureide, (17) alkyloxycarbonylamino or aryloxycarbonylamino, (18) alkylaminocarbonyloxy or arylaminocarbonyloxy, (19) cyano, (20) cyclic amino, and (21) a halogen atom; and

(IV) optionally halogenated alkyloxy, (V) cycloalkyl, (VI) aryl, (VII) aryloxy, (VIII) acylamino, (IX) acyloxy, (X) hydroxy, (XI) nitro, (XII) cyano, (XIII) amino, (XIV) monoalkylamino or dialkylamino, (XV) arylamino, (XVI) alkylsulfonylamino or arylsulfonylamino, (XVII) alkylureide or arylureide, (XVIII) alkyloxycarbonylamino or aryloxycarbonylamino, (XIX) alkylaminocarbonyloxy or arylaminocarbonyloxy, (XX) alkyloxycarbonyl or aryloxycarbonyl, (XXI) acyl, (XXII) carboxyl, (XXIII) carbamoyl, (XXIV) monoalkylcarbamoyl or dialkylcarbamoyl, (XXV) cyclic amino, and (XXVI) alkylsulfonyl or arylsulfonyl, and

R6 and R7 are each independently a hydrogen atom, a halogen atom, chloromethyl, hydroxymethyl, cyano, trifluoromethoxy, or a group represented by formula [3];

wherein

n is 0 to 5;

Q is an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl; and

R10 is a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino, dialkylamino, aryloxy, arylthio, cyano, nitro, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, acyl, aryl, optionally halogenated or alkylated aryl, cyclic amino, optionally halogenated or alkylated heterocycle, carboxylalkylcarbamoyl, monohydroxyalkyl, dihydroxyalkyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, heterocyclylalkylaminocarbonyl, alkylcarbonylamino, alkylcarbonyl, sulfonic acid, alkenyl, carboxylalkylcarbamoylalkyl, caboxylalkyl, 2-amino-2-alkoxycarbonylalkyl and heterocyclylcarbonylamino,

or a group represented by formula [4];

wherein

n and m are each 0 to 5; and

R11 and R12 are each independently a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino, dialkylamino, aryloxy, arylthio, hydroxy, cyano, nitro, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, acyl, optionally halogenated or alkylated aryl, cyclic amino, and optionally halogenated or alkylated heterocycle;

or R11 and R12 may together form a five- to nine-membered optionally halogenated or alkylated heterocycle containing, in addition to a nitrogen atom, 1 to 3 oxygen atoms or sulfur atoms.

2. A compound represented by general formula [1] or salt thereof:

wherein

R1 is an optionally substituted aryl or aromatic heterocycle; and

R2 is a halogen atom or lower alkyl optionally substituted by one or more substituents independently selected from (I) alkyloxy, (II) alkylthio, (III) alkylamino, (IV) cyano, (V) nitro, (VI) cyclic amino, and (VII) a halogen atom;

R3 represents a hydrogen atom, lower alkyl, or alkyl halide;

R4 represents a group selected from (I) optionally substituted phenyl, aryl, or heterocycle, (II) substituted or nonsubstituted alkyl, and (III) substituted or nonsubstituted alkenyl,

alternatively, R3 and R4 may form a five- to ten-membered cyclic structure together with a carbon atom to which they bind; and

X represents an oxygen atom or a sulfur atom,

provided that, when R3 is a hydrogen atom, then R4 represents a group other than methyl.

6. The compound or salt thereof according to claim 2, wherein the compound is represented by general formula [5]:

wherein

R2, R3, and R4 are as defined in claim 3;

Y and Z are each independently a carbon atom or a nitrogen atom;

R5, R6, R7, R8, and R9 are each independently selected from;

(I) a hydrogen atom;

(II) a halogen atom;

(III) lower alkyl optionally substituted by one or more substituents independently selected from (1) hydroxy, (2) amino, (3) alkyloxy, (4) alkylthio, (5) alkylsulfinyl, (6) alkylsulfonyl, (7) monoalkylamino or dialkylamino, (8) acyloxy, (9) acylamino, (10) aryloxy, (11) arylthio, (12) arylsulfinyl, (13) arylsulfonyl, (14) arylamino, (15) alkylsulfonylamino or arylsulfonylamino, (16) alkylureide or arylureide, (17) alkyloxycarbonylamino or aryloxycarbonylamino, (18) alkylaminocarbonyloxy or arylaminocarbonyloxy, (19) cyano, (20) cyclic amino, and (21) a halogen atom;

(IV) optionally halogenated alkyloxy;

(V) cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) acylamino;

(IX) acyloxy;

(X) hydroxy;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) monoalkylamino or dialkylamino;

(XV) arylamino;

(XVI) alkylsulfonylamino or arylsulfonylamino;

(XVII) alkylureide or arylureide;

(XVIII) alkyloxycarbonylamino or aryloxycarbonylamino;

(XIX) alkylaminocarbonyloxy or arylaminocarbonyloxy;

(XX) alkyloxycarbonyl or aryloxycarbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) monoalkylcarbamoyl or dialkylcarbamoyl;

(XXV) cyclic amino; and

(XXVI) alkylsulfonyl or arylsulfonyl;

provided that, when Y is a nitrogen atom, R6 is absent, and Z is a nitrogen atom, then R7 is absent.

7. The compound or salt thereof according to claim 2, wherein

R2 is methyl or ethyl;

R3 is a hydrogen atom, methyl, or trifluoromethyl;

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, cycloalkyl, aryl, aryloxy, acylamino, acyloxy, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, arylamino, alkylsulfonylamino, arylsulfonylamino, alkylureide, or arylureide, alkyloxycarbonylamino, aryloxycarbonylamino, alkylaminocarbonyloxy, arylaminocarbonyloxy, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, cyclic amino, alkylsulfonyl and arylsulfonyl;

R1 is a group represented by the following formula;

Y and Z are each independently a carbon atom; and

R5, R8, and R9 are each independently a group selected from;

(I) a hydrogen atom;

(II) a halogen atom;

(III) lower alkyl optionally substituted by one or more substituents independently selected from (1) hydroxy, (2) amino, (3) alkyloxy, (4) alkylthio, (5) alkylsulfinyl, (6) alkylsulfonyl, (7) monoalkylamino or dialkylamino, (8) acyloxy, (9) acylamino, (10) aryloxy, (11) arylthio, (12) arylsulfinyl, (13) arylsulfonyl, (14) arylamino, (15) alkylsulfonylamino or arylsulfonylamino, (16) alkylureide or arylureide, (17) alkyloxycarbonylamino or aryloxycarbonylamino, (18) alkylaminocarbonyloxy or arylaminocarbonyloxy, (19) cyano, (20) cyclic amino, and (21) a halogen atom;

(IV) optionally halogenated alkyloxy;

(V) cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) acylamino;

(IX) acyloxy;

(X) hydroxy;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) monoalkylamino or dialkylamino;

(XV) arylamino;

(XVI) alkylsulfonylamino or arylsulfonylamino;

(XVII) alkylureide or arylureide;

(XVIII) alkyloxycarbonylamino or aryloxycarbonylamino;

(XIX) alkylaminocarbonyloxy or arylaminocarbonyloxy;

(XX) alkyloxycarbonyl or aryloxycarbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) monoalkylcarbamoyl or dialkylcarbamoyl;

(XXV) cyclic amino; and

(XXVI) alkylsulfonyl or arylsulfonyl; and

R6 and R7 are each independently a hydrogen atom, a halogen atom, chloromethyl, hydroxymethyl, cyano, trifluoromethoxy, or a group represented by formula [3];

wherein

n is 0 to 5;

Q is an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl; and

R10 is a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino, dialkylamino, aryloxy, arylthio, cyano, nitro, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, acyl, aryl, cyclic amino, and heterocycle,

or a group represented by formula [4];

wherein

n and m are each 0 to 5; and

R11 and R12 are each independently a group selected from a hydrogen atom, a halogen atom, alkyl, alkyloxy, alkylthio, monoalkylamino, dialkylamino, aryloxy, arylthio, hydroxy, cyano, nitro, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, acyl, aryl, cyclic amino, and heterocycle;

or R11 and R12 may together form a five- to nine-membered heterocycle containing, in addition to a nitrogen atom, 1 to 3 oxygen atoms or sulfur atoms.

10. The compound or salt thereof according to claim 2, wherein X is an oxygen atom.

12. The compound or salt thereof according to claim 6, wherein

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, acylamino, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, and cyclic amino.

13. The compound or salt thereof according to claim 7, wherein

R4 is phenyl optionally substituted by one or more substituents independently selected from a halogen atom, optionally halogenated lower alkyl, optionally halogenated alkyloxy, optionally halogenated alkylthio, acylamino, hydroxy, nitro, cyano, amino, monoalkylamino, dialkylamino, alkyloxycarbonyl, aryloxycarbonyl, acyl, carboxyl, and cyclic amino.

15. The compound or salt thereof according to claim 6, wherein R4 is nonsubstituted phenyl, 2-chlorophenyl, 2-bromophenyl, or 2-fluorophenyl.

16. The compound or salt thereof according to claim 7, wherein R4 is nonsubstituted phenyl, 2-chlorophenyl, 2-bromophenyl, or 2-fluorophenyl.

18. A compound selected from:

3-Furylmethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

Benzyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-methyl-3-(4-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-methyl-3-(4-nitrophenyl)-4-isoxazolyl]carbamate;

Benzyl N-(3-methyl-5-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[3-[4-(hydroxymethyl)phenyl]-5-methyl-4-isoxazolyl]carbamate;

(1R)-1-Phenylethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

(1S)-1-Phenylethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-methyl-3-[4-(trifluoromethoxy)phenyl]-4-isoxazolyl]carbamate;

1-Phenylethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[3-(3-bromophenyl)-5-methyl-4-isoxazoly]carbamate;

1-(2-Methylphenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-methyl-3-[3-(trifluoromethyl)phenyl]-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-(4-fluorophenyl)-5-methyl-4-isoxazolyl]carbamate;

(1R)-1-(2-Chlorophenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

(1R)-1-(2-Chlorophenyl)ethyl N-(3-methyl-5-phenyl-4-isoxazolyl)carbamate;

1-(2-Fluorophenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[3-(2-fluorophenyl)-5-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-(3-fluorophenyl)-5-methyl-4-isoxazolyl]carbamate;

(1R)-1-(2-Bromophenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Bromophenyl)ethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

(1R)-1-(2-Bromophenyl)ethyl N-[3-chloro-5-(2-chlorophenyl)-4-isothiazolyl]carbamate;

1-Phenylethyl N-[3-chloro-5-(2-chlorophenyl)-4-isothiazolyl]carbamate;

1-(2-Fluorophenyl)ethyl N-[3-chloro-5-(2-chlorophenyl)-4-isothiazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(3-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(3-methylphenyl)-4-isoxazoly]carbamate;

1-Phenylethyl N-(5-(3-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(3-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-(2-furyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(2-furyl)-3-methyl-4-isoxazolyl]carbamate;

(1R)-1-(2-Bromophenyl)ethyl N-[5-(3-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Fluorophenyl)ethyl N-[5-(3-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-[4-(trifluoromethoxy)phenyl]-3-methyl-4-isoxazoly]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-[4-(trifluoromethoxy)phenyl]-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(4-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(3-chlorophenyl )-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-(4-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-fluorophenyl )-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-(2-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(2-fluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

(1R)-1-(2-Bromophenyl)ethyl N-[3-methyl-5-[4-(trifluoromethoxy)phenyl]-4-isoxazolyl]carbamate;

1-(2-Fluorophenyl)ethyl N-[3-methyl-5-[4-(trifluoromethoxy)phenyl]-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-(4-cyanophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-cyanophenyl)-3-methyl-4-isoxazolyl]carbamate;

(1R)-1-(2-Bromophenyl)ethyl N-[3-methyl-5-(4-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Fluorophenyl)ethyl N-[3-methyl-5-(4-methylphenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-methoxyphenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(2-bromophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(1,3-benzodioxol-5-yl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-[3-(trifluoromethoxy)phenyl]-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(4-nitrophenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-nitrophenyl)-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(2-thienyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(2-thienyl)-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(3-nitrophenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(3-nitrophenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(2,4-difluorophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(4-pyridyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-pyridyl)-4-isoxazoly]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(6-chloro-3-pyridyl)-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[5-(4-butylphenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-butylphenyl)-3-methyl-4-isoxazolyl]carbamate;

1-Phenylethyl N-[3-methyl-5-(3-methyl-2-thienyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(3-methyl-2-thienyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(3-furyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(5-methyl-2-thienyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-[3-(chloromethyl)phenyl]-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(2-chloro-4-pyridyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(3-phenyl-5-methyl-4-isoxazolyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(5-bromo-2-furyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-[4-(chloromethyl)phenyl]-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(3-thienyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(3-ethyl-5-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-cyanophenyl)-3-ethyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-(methoxymethyl)-5-phenyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-[4-(phenoxymethyl)phenyl]-4-isoxazolyl]carbamate;

2,2,2-Trifluoro-1-phenylethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-Phenylallyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-[[(4-fluorobenzyl)oxy]methyl]phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-[[(2,6-difluorobenzyl)oxy]methyl]phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(5-[4-[(2-furylmethoxy)methyl]phenyl]-3-methyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(5-[4-[(3-furylmethoxy)methyl]phenyl]-3-methyl-4-isoxazolyl)carbamate;

2,2,2-Trifluoro-1-phenylethyl N-[5-(4-cyanophenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-[4-(methoxymethyl)phenyl]-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-[4-(morpholinomethyl)phenyl]-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(5-[4-[(2,6-dimethylmorpholino)methyl]phenyl]-3-methyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-[4-[([2-(2-pyridyl)ethyl]amino)methyl]phenyl]-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-[[(tetrahydro-2-furanylmethyl)amino]-methyl]phenyl)-4-isoxazolyl]-carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-[[(2-pyridylmethyl)amino]methyl]phenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-[[(2-furylmethyl)amino]methyl]phenyl)-3-methyl-4-isoxazolyl]carbamate;

2-cyclohexyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

2-Methylphenethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

Phenethyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

2,3-Dihydro-1H-1-indenyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1,2,3,4-Tetrahydro-2-naphthalenyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

Pentyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

Isopentyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-Methylpentyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

4-Pentenyl N-(5-methyl-3-phenyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-{3-methyl-5-[4-({[2-(2-pryidyl)ethyl]amino}methyl)phenyl]-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-{[(tetrahydro-2-furanylmethyl)amino]-methyl}phenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl]ethyl N-[3-methyl-5-(4-{[(2-pyridylmethyl)amino]methyl}-phenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-{[(2-furylmethyl)amino]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-{[(2-furylmethyl)sulfanyl]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(5-{4-[(ethylsulfanyl)methyl]phenyl}-3-methyl-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{4-[(pentylamino)methyl]phenyl}-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-{3-methyl-5-[4-({[2-(3-pyridyl)ethyl]amino}methyl)-phenyl]-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-{3-methyl-5-[4-({[2-(4-pyridyl)ethyl]amino}methyl)phenyl]-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-{[(2-fluoroethyl)amino]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

Ethyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}amino)propanoate;

1-(2-Chlorophenyl)ethyl N-{3-methyl-5-[4-({[(5-methyl-2-pyrazyl)methyl]amino}-methyl)phenyl]-4-isoxazolyl}carbamate;

Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate;

1-(2-Chlorophenyl)ethyl N-(5-{4-[(ethylamino)methyl]phenyl}-3-methyl-4-isoxazolyl)-carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{4-[(propylsulfanyl)methyl]phenyl}-4-isoxazolyl)carbamate;

Methyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}-amino)-3-methyl-5-isoxazolyl]-benzyl}-sulfanyl)acetate;

Ethyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)acetate;

1-(2-Chlorophenyl)ethyl N-[5-(4-{[(2-hydroxyethyl)sulfanyl]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

2-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)acetic acid;

1-(2-Chlorophenyl)ethyl N-{5-[4-({[(2R)-2-amino-3-ethyl-3-butenyl]sulfanyl}methyl)-phenyl]-3-methyl-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-(5-{4-[(allylsulfanyl)methyl]phenyl}-3-methyl-4-isoxazolyl)-carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{4-[(phenethylsulfanyl)methyl]phenyl}-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-(5-{4-[(butylsulfanyl)methyl]phenyl}-3-methyl-4-isoxazolyl)-carbamate;

3-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

N-[2-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)propanoyl]carbamic acid;

1-(2-Chlorophenyl)ethyl N-{5-[3-(methoxymethyl)phenyl]-3-methyl-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-{5-[3-(ethoxymethyl)phenyl]-3-methyl-4-isoxazolyl}carbamate;

Methyl 2-({3-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfanyl)acetate;

1-(2-Chlorophenyl)ethyl N-[5-(3-{[(2-hydroxyethyl)sulfanyl]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(5-{3-[(ethylsulfanyl)methyl]phenyl}-3-methyl-4-isoxazolyl)carbamate;

Methyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}-sulfonyl)acetate;

Methyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}sulfinyl)acetate;

1(2-Chlorophenyl)ethyl N-[5-(4-{[(2,3-dihydroxypropyl)sufanyl]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{4-[(1H-1,2,4-triazol-3-ylsulfanyl)methyl]-phenyl}-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[3-methyl-5-(4-{[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)-sulfanyl]methyl}phenyl)-4-isoxazolyl]carbamate;

1-(2-Chlorophenyl)ethyl N-{3-methyl-5-[4-({[2-(methylamino)-2-oxoethyl]sulfanyl}-methyl)phenyl]-4-isoxazolyl}carbamate;

1-(2-Chlorophenyl)ethyl N-(5-{4-[({2-[(2-furylmethyl)amino]-2-oxoethyl}sulfanyl) -methyl]phenyl}-3-methyl-4-isoxazolyl)carbamate;

Ethyl 2-({3-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)acetate;

1-(2-Chlorophenyl)ethyl N-(5-{3-[(allylsulfanyl)methyl]phenyl}-3-methyl-4-isoxazolyl)-carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{3-[(phenethylsulfanyl)methyl]phenyl}-4-isoxazolyl)-carbamate;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{3-[(1H-1,2,4-triazol-3-ylsulfanyl)methyl]phenyl}-4-isoxazolyl)carbamate;

4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl ethanethioate;

1-(2-Chlorophenyl)ethyl N-{5-[4-({[2-(acetylamino)ethyl]sulfanyl}methyl)phenyl]-3-methyl-4-isoxazolyl}carbamate;

Methyl 3-({4-[4-({[1-(2-chlorophenyl)ethoxyl]carbonyl}amino)-3-ethyl-5-isoxazolyl]-benzyl}sulfanyl)propanoate;

3-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-ethyl-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

2-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

1-(2-Chlorophenyl)ethyl N-(3-methyl-5-{4-[({2-[(1H-2-pyrrolylcarbonyl)amino]ethyl}-sulfanyl)methyl]phenyl}-4-isoxazolyl)carbamate;

1-(2-Chlorophenyl)ethyl N-[5-(4-{[(2-chloroethyl)sulfanyl]methyl}phenyl)-3-methyl-4-isoxazolyl]carbamate;

2-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)-1-ethanesulfonic acid;

3-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)-1-propanesulfonic acid;

Methyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-ethyl-5-isoxazolyl]benzyl}-sulfanyl)acetate;

2-({4-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-ethyl-5-isoxazolyl]benzyl}-sulfanyl)acetic acid;

1-(2-Fluorophenyl)ethyl N-{5-[4-(chloromethyl)phenyl]-3-methyl-4-isoxazolyl}carbamate;

Methyl 3-({4-[4-({[1-(2-fluorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}-sulfanyl)propanoate;

3-({4-[4-({[1-(2-Fluorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

2-({3-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)-1-ethanesulfonic acid;

3-({3-[4-({[1-(2-Chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

1-(2-Fluorophenyl)ethyl N-{5-[4-(chloromethyl)phenyl]-3-ethyl-4-isoxazolyl}carbamate;

2,2,2-Trifluoro-1-phenylethyl N-{5-[4-(chloromethyl)phenyl]-3-methyl-4-isoxazolyl}-carbamate;

Methyl 3-{[4-(3-methyl-4-[(2,2,2-trifluoro-1-phenylethoxy)carbonyl]amino}-5-isoxazolyl)-benzyl]-sulfanyl}propanoate;

3-{[4-(3-Methyl-4-{[(2,2,2-trifluoro-1-phenylethoxy)carbonyl]amino}-5-isoxazolyl)benzyl]-sulfanyl}propanoic acid;

2,2,2-Trifluoro-1-phenylethyl N-{5-[4-(chloromethyl)phenyl]-3-ethyl-4-isoxazolyl}carbamate;

Methyl 3-({4-[3-ethyl-4-({[1-(2-fluorophenyl)ethoxy]carbonyl}amino)-5-isoxazolyl]-benzyl}sulfanyl)propanoate;

Methyl 3-{[4-(3-ethyl-4-{[(2,2,2-trifluoro-1-phenylethoxy)carbonyl]amino}-5-isoxazolyl)-benzyl]sulfanyl}propanoate;

3-({4-[3-Ethyl-4-({[1-(2-fluorophenyl)ethoxy]carbonyl}amino)-5-isoxazolyl]benzyl}-sulfanyl)propanoic acid;

Ethyl 2-({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-5-isoxazolyl]-benzyl}oxy)acetate; and

Ethyl 2-{[4-(3-methyl-4-{[(2,2,2-trifluoro-1-phenylethoxy)carbonyl]amino}-5-isoxazolyl)-benzyl]oxy}acetate;

or salt thereof.