IP Library › Granted Patent US 8,822,467

Granted Patent B2

US 8,822,467 · App. 13/715,754 · Granted Sep 2, 2014

Biaryl oxyacetic acid compounds

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Quick Facts

Patent No.: US 8,822,467
App. No.: 13/715,754
Granted: Sep 2, 2014
Kind: B2

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Abstract

The present invention provides biaryl oxyacetic acid compounds which may be useful for treating inflammatory disorders, including disorders affecting the respiratory system and skin. The compounds provided include those of the general formula I:

Claims (477)

1. A compound of formula I

or salt thereof

wherein

R 1 , R 2 , R 3 and R 4 are each independently selected from hydrogen and (C 1 -C 6 ) alkyl;

R 5 is selected from hydrogen, (C 1 -C 6 ) alkyl and (C 3 -C 8 ) cycloalkyl;

R 6 is selected from:

a. (C 1 -C 4 ) alkyl,

b. (C 3 -C 8 ) cycloalkyl,

c. dialkylamino,

d. alkylamino, and

e. aryl, heteroaryl and arylalkyl, each optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkyl, and (C 1 -C 6 ) alkylsulfonyl;

R 7a is selected from hydrogen and fluoro;

R 7b is selected from hydrogen, fluoro and chloro;

R 7c is selected from hydrogen, fluoro and chloro;

A is selected from aryl and heteroaryl; and

W, X, Y and Z are each independently selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, hydroxy, (C 1 -C 6 ) alkoxyalkyl, (C 1 -C 6 ) alkylsulfonyl, (C 1 -C 6 ) alkylaminosulfonyl, carboxamido, cyano, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) alkoxycarbonyl, aminosulfonyl, dialkylaminosulfonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclylcarbonyl, heterocyclylacyl, heterocyclylalkyl, and heterocyclyl optionally substituted with (C 1 -C 6 ) alkyl;

with the proviso that, when A is phenyl or pyridinyl substituted at the ortho position, any of W, X, Y and Z at said ortho position are each independently selected from hydrogen and halogen.

2. A compound or salt according to claim 1 wherein R 1 , R 2 , R 3 and R 4 are each independently selected from hydrogen and methyl.

3. A compound or salt according to claim 1 , wherein R 5 is selected from hydrogen, methyl, ethyl, propyl and isopropyl.

4. A compound or salt according to claim 1 , wherein R 6 is selected from aryl and heteroaryl, each optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkyl, and (C 1 -C 6 ) alkylsulfonyl.

5. A compound or salt according to claim 4 , wherein

R 6 is

R 8 is selected from hydrogen, halogen, (C 1 -C 6 ) alkyl, cyano, (C 1 -C 6 ) haloalkyl, and (C 1 -C 6 ) alkoxy;

R 9 is selected from hydrogen, halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkoxy, cyano, (C 1 -C 6 ) haloalkyl and (C 1 -C 6 ) alkylsulfonyl;

R 10 is selected from hydrogen, halogen, (C 1 -C 6 ) alkoxy and (C 1 -C 6 ) alkyl; and

R 11 is selected from hydrogen, halogen, alkoxy and (C 1 -C 6 ) alkyl.

6. A compound or salt according to claim 5 wherein R 6 is

7. A compound or salt according to claim 6 , wherein R 8 is selected from hydrogen, methyl, fluoro, chloro, cyano, —CF 3 and methoxy; and R 9 is selected from hydrogen, fluoro, chloro, methyl, methoxy, cyano, —CF 3 and —SO 2 CH 3 .

8. A compound or salt according to claim 7 wherein R 8 and R 9 are each independently selected from fluoro, chloro, methoxy and hydrogen.

9. A compound or salt according to claim 5 wherein R 6 is

10. A compound or salt according to claim 4 wherein R 6 is selected from naphthyl, pyridinyl and quinolinyl, each optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkyl and alkylsulfonyl.

11. A compound or salt according to claim 1 , wherein R 7a and R 7b are each hydrogen.

12. A compound or salt according to claim 1 , wherein A is selected from phenyl, pyridinyl, benzimidazolyl, quinolinyl, indolyl, pyrimidinyl and imidazopyridinyl.

13. A compound or salt according to claim 12 , wherein A is phenyl or pyridinyl.

14. A compound or salt according to claim 13 , wherein

W is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen and haloalkyl;

X is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, haloalkyl, haloalkoxy, alkoxy, aminosulfonyl, alkoxycarbonyl, heterocyclylcarbonyl, hydroxy, alkoxyalkyl, alkylsulfonyl, alkylaminosulfonyl, carboxamido, cyano, and heterocyclyl optionally substituted with (C 1 -C 6 ) alkyl; and

Y and Z are both hydrogen.

15. A compound or salt according to claim 14 , wherein

W is selected from hydrogen, fluoro, chloro, methyl and trifluoromethyl; and

X is selected from hydrogen, trifluoromethyl, chloro, fluoro, bromo, methoxy, hydroxy, trifluoromethoxy, propyl, ethyl, methyl, methoxymethyl, cyano, carboxamido, heterocyclylcarbonyl, methylsulfonyl, ethylsulfonyl, propoxy, ethoxy, methoxy, methylaminocarbonyl, dimethylaminocarbonyl, dimethoxycarbonyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.

16. A compound or salt according to claim 15 wherein W and X are in the meta positions in relation to the attachment of the ring A.

17. A compound or salt according to claim 15 wherein W is substituted in the meta position and X is substituted in the para position in relation to the attachment of the ring A.

18. A compound or salt according to claim 1 , wherein

R 1 , R 2 , R 3 and R 4 are each hydrogen;

R 5 is methyl;

R 6 is phenyl optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) alkyl and (C 1 -C 6 ) alkylsulfonyl;

R 7a is hydrogen;

R 7b is selected from hydrogen, fluoro and chloro;

R 7c is hydrogen; and

A is selected from phenyl and pyridinyl.

19. A compound or salt according to claim 18 , wherein

R 6 is

R 8 is selected from hydrogen, fluoro, chloro, methyl, cyano, —CF 3 and methoxy;

R 9 is selected from hydrogen, fluoro, chloro, methyl, methoxy, cyano, —CF 3 , and —SO 2 CH 3 ;

W is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, and haloalkyl;

X is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, haloalkyl, haloalkoxy, hydroxy, alkoxy, alkoxyalkyl, alkylsulfonyl, alkylaminosulfonyl, carboxamido, cyano, and heterocyclylalkyl; and

Y and Z are each hydrogen.

20. A compound or salt according to claim 19 , wherein

R 8 is selected from hydrogen, fluoro, chloro and methyl;

A is phenyl;

W is selected from hydrogen and fluoro and is in the meta position in relation to the attachment of the ring A; and

X is selected from alkylsulfonyl, fluoro, alkylaminosulfonyl and cyano and is in the meta position in relation to the attachment of the ring A.

21. A compound according to formula Ia

or salt thereof, wherein

R 1 , R 2 , R 3 and R 4 are each independently selected from hydrogen and (C 1 -C 6 ) alkyl;

R 5 is selected from hydrogen, (C 1 -C 6 ) alkyl, and cycloalkyl;

R 6 is selected from

a. (C 1 -C 4 ) alkyl,

b. (C 3 -C 8 ) cycloalkyl,

c. dialkylamino,

d. alkylamino, and

R 7a is selected from hydrogen and fluoro;

R 7b is selected from hydrogen, fluoro, and chloro;

R 7c is selected from hydrogen, fluoro, and chloro;

Q is selected from N and CX′;

J is selected from N and CY′, wherein both Q and J cannot be N;

X 1 , X′ and Z 1 are each independently selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, hydroxy, (C 1 -C 6 ) alkoxyalkyl, (C 1 -C 6 ) alkylsulfonyl, (C 1 -C 6 ) alkylaminosulfonyl, carboxamido, cyano, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) alkoxycarbonyl, aminosulfonyl, dialkylaminosulfonyl, alkylaminocarbonyl, dialkylaminocarbonyl, heterocyclylcarbonyl, heterocyclylacyl, heterocyclylalkyl, and heterocyclyl optionally substituted with (C 1 -C 6 ) alkyl; and

Y 1 and Y′ are each independently selected from hydrogen and halogen.

22. A compound or salt according to claim 21 wherein R 1 , R 2 , R 3 and R 4 are each independently selected from hydrogen and methyl.

23. A compound or salt according to claim 21 , wherein R 5 is selected from hydrogen, methyl, ethyl, propyl and isopropyl.

24. A compound or salt according to claim 21 , wherein R 6 is selected from aryl and heteroaryl, each optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkyl, and (C 1 -C 6 ) alkylsulfonyl.

25. A compound or salt according to claim 24 , wherein

R 6 is

R 8 is selected from hydrogen, halogen, (C 1 -C 6 ) alkyl, cyano, (C 1 -C 6 ) haloalkyl, and (C 1 -C 6 ) alkoxy;

R 9 is selected from hydrogen, halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, cyano, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) haloalkyl, and (C 1 -C 6 ) alkylsulfonyl;

R 10 is selected from hydrogen, halogen, (C 1 -C 6 ) alkoxy, and (C 1 -C 6 ) alkyl; and

R 11 is selected from hydrogen, halogen, (C 1 -C 6 ) alkoxy, and (C 1 -C 6 ) alkyl.

26. A compound or salt according to claim 25 , wherein R 6 is

27. A compound or salt according to claim 26 , wherein

R 8 is selected from hydrogen, methyl, fluoro, chloro, cyano, —CF 3 , and methoxy; and

R 9 is selected from hydrogen, fluoro, chloro, methyl, methoxy, cyano, —CF 3 , and —SO 2 CH 3 .

28. A compound or salt according to claim 25 , wherein R 6 is

29. A compound or salt according to claim 24 , wherein R 6 is selected from naphthyl, pyridinyl and quinolinyl, each optionally substituted with one to four substituents independently selected from halogen, cyano, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) alkyl, and (C 1 -C 6 ) alkylsulfonyl.

30. A compound or salt according to claim 21 , wherein R 7a and R 7c are each hydrogen.

31. A compound or salt according to claim 21 , wherein Q is CX′ and J is CY′.

32. A compound or salt according to claim 31 , wherein X′ is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen and haloalkyl; and Y′ is hydrogen.

33. A compound or salt according to claim 21 , wherein Z 1 is selected from hydrogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkylsulfonyl, halogen, and haloalkyl.

34. A compound or salt according to claim 24 , wherein

R 1 , R 2 , R 3 and R 4 are each hydrogen;

R 5 is methyl; and

R 6 is phenyl optionally substituted with one to four substituents independently selected from halogen, cyano, haloalkyl, (C 1 -C 6 ) haloalkoxy, alkoxy, (C 1 -C 6 ) alkyl, and alkylsulfonyl.

35. A compound or salt according to claim 34 , wherein

R 6 is

R 8 is selected from hydrogen, fluoro, chloro, methyl, cyano, —CF 3 , and methoxy;

R 9 is selected from hydrogen, fluoro, chloro, methyl, methoxy, cyano, —CF 3 , and —SO 2 CH 3 ;

Q is CX′;

X′ is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, and haloalkyl; and

X 1 is selected from hydrogen, (C 1 -C 6 ) alkyl, halogen, haloalkyl, haloalkoxy, hydroxy, alkoxy, alkoxyalkyl, alkylsulfonyl, alkylaminosulfonyl, carboxamido, cyano, and heterocyclylalkyl.

36. A compound or salt according to claim 35 , wherein

R 8 is selected from hydrogen, fluoro, chloro and methyl;

J is CY′;

X′ is selected from hydrogen and fluoro;

X 1 is selected from alkoxy, alkylsulfonyl, fluoro, alkylaminosulfonyl and cyano; and

Z 1 is selected from hydrogen, fluoro, chloro, (C 1 -C 6 ) alkyl, alkylsulfonyl, and haloalkyl.

37. A compound or salt according to claim 21 , wherein Q is N and J is CY′.

38. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

39. A method of ameliorating a disorder responsive to inhibition of chemoattractant receptor-homologous molecule expressed on T helper 2, which comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 1 .

40. A method according to claim 39 , wherein said disorder is selected from the group consisting of an inflammatory disorder, a respiratory disorder, and a skin disorder.

41. A method according to claim 39 , wherein said disorder is selected from the group consisting of asthma, rhinitis, chronic obstructive pulmonary disease, bronchitis, nasal polyposis, nasal congestion, farmer's lung, fibroid lung, cough, dermatitis, cutaneous eosinophilias, Lichen planus, urticaria, psoriasis, pruritus, angiodermas, corneal ulcers, chronic skin ulcers, conjunctivitis, vasculitides, uveitis, erythemas, osteoarthritis, rheumatoid arthritis, pain, and inflammatory bowel disease.

42. A method according to claim 39 , wherein said subject is a human.

43. The compound of claim 1 selected from the group consisting of

2-(3-cyano-5-fluorophenyl)-4-((3-fluoro-4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methoxy-5-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-fluoro-5-methoxyphenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-N-methylsulfamoylphenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3,4-difluoro-phenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-N-methylsulfamoylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-fluoro-5-methoxyphenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-chloro-5-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-fluoro-5-methoxyphenyl)-4-((3-fluoro-4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-5-chlorophenoxyacetic acid,

2-(3-N-methylsulfamoylphenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3,5-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3,4-dichloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((2,3-dichloro-N-methylthiophene-5-sulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)-5-chlorophenoxyacetic acid,

2-(4-fluoro-3-(methylsulfonyl)phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-4-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-ethylsulfonylphenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3-fluoro-4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((4-methyl-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(5-benzo[c][1,2,5]oxadiazolyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((2-chloro-N-methylthiophene-5-sulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-4-methyl-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-methyl-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonyl-5-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((N-methylthiophene-2-sulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-aminosulfonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3,4-dichloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((3,5-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((N-methylphenylsulfonamido)methyl)-5-chlorophenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((4-fluoro-phenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-N,N-dimethylsulfamoylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((4-fluorophenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3-chloro-4-fluoro-phenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-ethylsulfonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-fluorophenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonyl-4-methyl-phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((4-cyano-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3,4-dichloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethyl-5-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((3-cyano-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(1-methyl-indol-6-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2-cyanothiophen-5-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3-methyl-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3,5-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-(1-(3,4-difluoro-N-methylphenylsulfonamido)ethyl)phenoxyacetic acid,

2-(3-methylsulfonylphenyl)-4-((2-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)-5-chlorophenoxyacetic acid,

2-(3-isopropoxy-5-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanoic acid,

2-(3-cyanophenyl)-4-((3-methoxy-4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methoxymethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-aminocarbonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((2,4-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((3-trifluoromethyl-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethoxyphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2,5-difluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-ethoxy-5-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3,4-difluoro-N-ethylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-chloro-5-fluorophenyl)-4-((-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2-chloro-5-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-isopropylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-cyano-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-6-fluorophenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2,3-difluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-(1-(4-fluoro-N-methylphenylsulfonamido)ethyl)phenoxyacetic acid,

2-(4-methylsulfonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(6-trifluoromethyl-2-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(imidazo[1,2-a]pyridin-7-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-hydroxyphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethyl-5-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methoxyphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-methylsulfonyl-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylpyridine-3-sulfonamido)methyl)phenoxyacetic acid,

2-(3-N-methylaminocarbonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3,5-difluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-difluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-6-fluorophenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-ethylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methoxycarbonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-bromophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylquinoline-8-sulfonamido)methyl)phenoxyacetic acid,

2-(3,4-difluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((2-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyanophenyl)-4-((4-methyl-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-dimethylaminocarbonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylnaphthalene-1-sulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylnaphthalene-2-sulfonamido)methyl)phenoxyacetic acid,

2-(4-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3,4-difluoro-N-isopropylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((3-methoxy-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

(R)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanoic acid,

2-(3,4-difluorophenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-chloro-4-fluorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-isopropylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(4-trifluoromethyl-pyridinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylbenzylsulfonamido)methyl)phenoxyacetic acid,

2-(isoquinolin-5-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N,3,5-trimethylisoxazole-4-sulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-6-fluorophenoxyacetic acid,

2-(3-chlorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(pyrazinyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(4-methoxyphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2,5-difluorophenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-chlorophenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(N-oxy-pyridine-3-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-phenyl-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((2-chloro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3,5-dimethylisoxazol-4-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(pyrimidin-5-yl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylpyridine-2-sulfonamido)methyl)phenoxyacetic acid,

2-((3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid,

2-(3-trifluoromethylphenyl)-4-((3,5-difluoro-N-isopropylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methyl-3H-benzo[d]imidazol-5-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-morpholinocarbonylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(4-chlorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(2-chlorophenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(4-chlorophenyl)-4-((N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(quinolin-5-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methylcyclopropanesulfonamido)methyl)phenoxyacetic acid,

2-(3-trifluoromethylphenyl)-4-((N-methyldimethylaminosulfonamido)methyl)phenoxyacetic acid,

2-phenyl-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(1H-indol-6-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-methoxyphenyl)-4-((-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(1-methyl-1H-pyrazol-4-yl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-4-((3-fluoro-4-methoxyphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluorophenyl)-(5-fluoro-4-((3-fluoro-4-methoxy-N-methylphenylsulfonamido)methyl)phenoxy)acetic acid,

2-(3-cyano-5-chloro-phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxyacetic acid,

2-(3-cyano-5-fluoro-phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyano-5-fluoro-phenyl)-4-((3-chloro-4-fluoro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyano-5-fluoro-phenyl)-4-((3-chloro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyano-5-fluoro-phenyl)-4-((3,4-dichloro-N-methylphenylsulfonamido)methyl)-5-fluorophenoxyacetic acid,

2-(3-cyano-5-fluoro-phenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)-5-chlorophenoxyacetic acid, and a salt thereof.

44. The compound of claim 1 selected from the group consisting of