Modulators of PPAR and methods of their preparation
The present invention is directed to certain novel compounds represented by Formula (I) and pharmaceutically acceptable salts, solvates, hydrates and prodrugs thereof. The present invention is also directed to methods of making and using such compounds and pharmaceutical compositions containing such compounds to treat or control a number of diseases mediated by PPAR such as glucose metabolism, lipid metabolism and insulin secretion, specifically Type 2 diabetes, hyperinsulinemia, hyperlipidemia, hyperuricemia, hypercholesteremia, atherosclerosis, one or more risk factors for cardiovascular disease, Syndrome X, hypertriglyceridemia, hyperglycemia, obesity and eating disorders.
1. A compound having the formula:
Z—K—Ar 1 —L—Ar 2 —R 1 (I)
wherein
Ar 1 is selected from the group consisting of benzene, imidazole, indole and indazole, each of which is optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
Ar 2 is benzene, which is optionally substituted with from one to two R 4 substituents;
K is absent or is a linking group selected from the group consisting of —CH 2 —, —CH 2 CH 2 , —CH 2 O—, —CH(CH 3 )O—, —C(CH 3 ) 2 O—, —CH(CH 3 )—, —CH(OCH 3 )— and —C(CH 3 ) 2 — wherein K can be attached to any available ring member of Ar 1 ;
L is a linking group joining Ar 1 and Ar 2 and is selected from the group consisting of —O(CH 2 ) 3 O—, —O(CH 2 ) 2 O—, —S(CH 2 ) 3 O—, and —S(CH 2 ) 2 O— wherein L can be attached to any available ring member of Ar 1 and to any available ring member of Ar 2 ;
Z is CO 2 R 8 ;
R 1 is a member independently selected from the group consisting of:
each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 , (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, aryl, aryl(C 1 -C 4 )alkyl, aryl(C 2 -C 8 )alkenyl, aryl(C 2 -C 8 )alkynyl, heterocyclyl, heterocyclyl(C 1 -C 4 )alkyl, —COR 7 , —CO 2 R 7 , —NR 7 R 24 , —NO 2 , —CN, —S(O) r1 R 7 , −X 1 OR 7 , —X 1 COR 7 , —X 1 CO 2 R 7 , —X 1 NR 7 R 24 , —X 1 NO 2 , —X 1 CN and —X 1 S(O) r1 R 7 ;
each R 4 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 , (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, aryl(C 1 -C 4 )alkyl, aryl(C 2 -C 8 )alkenyl, aryl(C 2 -C 8 )alkynyl, heterocyclyl, heterocyclyl(C 1 -C 4 )alkyl, —COR 7 , —CO 2 R 7 , —NR 7 R 24 , —NO 2 , —CN, —S(O) r1 R 7 , —X 2 OR 7 , —X 2 COR 7 , —X 2 CO 2 R 7 , —X 2 NR 7 R 24 , —X 2 NO 2 , —X 2 CN, —X 2 S(O) r1 R 7 ,
each ring of which is optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl;
each R 7 and R 24 is a member independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —X 3 OR 25 , —CO, aryl, aryl(C 1 -C 4 )alkyl and heteroaryl or optionally, if both are present on the same substituent, may be joined together to form a three- to eight-membered ring;
each R 8 is a member independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —X 4 OR 7 , —X 4 NR 7 R 24 , (C 2 -C 8 )alkenyl, (C 3 -C 7 )cycloalkyl, heterocyclyl, heteroaryl, aryl, aryl(C 1 -C 4 )alkyl and aryl(C 2 -C 8 )alkenyl
each R 9 or R 10 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the triazole ring to form a triazolopyridine, benzotriazole or tetrahydrobenzotriazole ring optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each R 11 or R 12 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the imidazole ring to form a benzimidazolyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each R 13 or R 14 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the oxazole ring to form a benzoxazolyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each R 15 or R 16 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the thiazole ring to form a benzothiazoyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each R 17 or R 18 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the pyrazole ring to form a indazoyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each R 19 or R 20 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the pyrrolidine ring to form a dihydroisoindole ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
R 21 is CH 3 , phenyl or pyridyl, wherein the phenyl and pyridyl substituents are, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
each of R 22 or R 23 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, —OR 7 , halo and (C 1 -C 9 )haloalkyl;
R 25 is a member selected from the group consisting of H, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 4 )alkyl and heteroaryl;
each W 1 or W 2 is independently N or CR 22 ;
each X 1 , X 2 , X 3 and X 4 is a member independently selected from the group consisting of (C 1 -C 4 )alkylene, (C 2 -C 4 )alkenylene and (C 2 -C 4 )alkynylene;
the subscript r1 is an integer of from 0 to 2; and
pharmaceutically acceptable salts thereof.
2. A compound of claim 1 , wherein R 8 is H.
3. A compound of claim 1 , wherein Ar 1 is selected from the group consisting of:
(i) an indole ring, optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof; and
(ii) an indazole ring , optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl and —OR 7 .
4. A compound of claim 1 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl and —OR 7 ; and the dashed line indicates the point of attachment to K and the wavy line indicates the point of attachment to L.
5. A compound of claim 1 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl and —OR 7 ; and the dashed line indicates the point of attachment to L and the wavy line indicates the point of attachment to K.
6. A compound of claim 4 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl and —OR 7 ; and the dashed line indicates the point of attachment to K and the wavy line indicates the point of attachment to L.
7. A compound of claim 5 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein the dashed line indicates the point of attachment to L and the wavy line indicates the point of attachment to K.
8. A compound of claim 6 , wherein the compound is
9. A compound of claim 4 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl and —OR 7 ; and the dashed line indicates the point of attachment to K and the wavy line indicates the point of attachment to L.
10. A compound of claim 5 , wherein Ar 1 is
optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein the dashed line indicates the point of attachment to L and the wavy line indicates the point of attachment to K.
11. A compound of claim 9 , wherein the compound is
12. A compound of claim 9 , wherein the compound is
13. A compound of claim 1 , wherein Ar 1 is benzene, optionally substituted with a R 2 substituent, a R 3 substituent or a combination thereof;
wherein each R 2 or R 3 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 .
14. A compound of claim 1 , wherein Ar 2 is
benzene, optionally substituted with from one to two R 4 substituents;
wherein each R 4 substituent is a member independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 ,
wherein the wavy line indicates the point of attachment to Ar 2 , each ring of which is optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl.
15. A compound of claim 14 , wherein Ar 2 has the formula:
which is optionally substituted with from one to two R 4 substituents wherein each R 4 substituent is a member independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 ,
each ring of which is optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl; wherein the dashed line indicates the point of 2 attachment to L and the wavy line indicates the point of attachment to Ar 2 .
16. A compound of claim 15 , wherein Ar 2 has the formula:
which is optionally substituted with from one to two R 4 substituents wherein each R 4 substituent is a member independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, —OR 7 ,
each ring of which is optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl; wherein the dashed line indicates the point of attachment to L and the wavy line indicates the point of attachment to Ar 2 .
17. A compound of claim 1 , wherein R 1 is a member selected from the group consisting of:
wherein
each R 9 or R 10 is independently CH 3 , halo or is joined together with the triazole ring to form a triazolopyridine, benzotriazole or tetrahydrobenzotriazole ring optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl;
each R 13 or R 14 is independently CH 3 , halo or is joined together with the oxazole ring to form a benzoxazolyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl;
each R 15 or R 16 is independently H, (C 1 -C 8 )alkyl, halo, (C 1 -C 8 )haloalkyl or is joined together with the thiazole ring to form a benzothiazoyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl;
R 22 is H, (C 1 -C 8 )alkyl, —OR 7 , halo or (C 1 -C 8 )haloalkyl;
R 23 is halo or (C 1 -C 9 )alkoxy;
W 1 is N or CR 22 ; and the wavy line indicates the point of attachment to the rest of the molecule.
18. A compound of claim 17 , wherein R 1 has the formula:
wherein
each R 9 or R 10 is independently CH 3 , halo or is joined together with the triazole ring to form a triazolopyridine, benzotriazole or tetrahydrobenzotriazole ring optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl.
19. A compound of claim 17 , wherein R 1 has the formula:
wherein
each R 13 or R 14 is independently CH 3 , halo or is joined together with the oxazole ring to form a benzoxazolyl ring , optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl.
20. A compound of claim 17 , wherein R 1 has the formula:
wherein
each R 15 or R 16 is independently H, (C 1 -C 8 )alkyl, halo, (C 1 -C 8 )haloalkyl or is joined together with the thiazole ring to form a benzothiazoyl ring , optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl.
21. A compound of claim 17 , wherein R 1 is a member selected from the group consisting of:
wherein
R 22 is H, (C 1 -C 8 )alkyl, —OR 7 , halo or (C 1 -C 8 )haloalkyl;
R 23 is halo or (C 1 -C 8 )alkoxy; and
W 1 is N or CR 22 .
22. A compound of claim 1 , wherein the compound is
23. A compound of claim 1 , wherein the compound is
24. A compound of claim 1 , wherein R 1 has the formula:
wherein
each R 13 or R 14 is CH 3 , halo or is joined together with the oxazole ring to form a benzoxazolyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl.
25. A compound of claim 24 , wherein the compound is
26. A compound of claim 24 , wherein the compound is
27. A compound of claim 24 , wherein the compound is
28. A compound of claim 24 , wherein the compound is
29. A compound of claim 24 , wherein the compound is
30. A compound of claim 1 , wherein R 1 has the formula:
wherein
each R 15 or R 16 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, halo and (C 1 -C 8 )haloalkyl or is joined together with the thiazole ring to form a benzothiazoyl ring, optionally substituted with from one to two substituents independently selected from the group consisting of —OR 7 , —CO 2 R 7 , —NR 7 R 24 , —CN, —S(O) r1 R 7 , halo, (C 1 -C 8 )alkyl and (C 1 -C 8 )haloalkyl.
31. A compound of claim 30 , wherein the compound is
32. A compound of claim 30 , wherein the compound is
33. A compound of claim 1 , wherein R 1 has the formula:
wherein
R 22 is H, (C 1 -C 8 )alkyl, —OR 7 , halo or (C 1 -C 8 )haloalkyl;
R 23 is halo or (C 1 -C 8 )alkoxy; and
W 1 is N or CR 22 .
34. A compound of claim 33 , wherein the compound is
35. A compound of claim 33 , wherein the compound is
36. A compound of claim 33 , wherein the compound is
37. A compound of claim 1 , wherein R 1 has the formula:
wherein
each R 9 or R 10 is CH 3 , halo or is joined together with the triazole ring to form a triazolopyridine, benzotriazole or tetrahydrobenzotriazole ring optionally substituted with from one to two substituents independently selected from the group consisting of halo and (C 1 -C 8 )alkyl.
38. A compound of claim 37 , wherein the compound is
39. A compound of claim 1 , wherein the compound is
40. A compound of claim 1 , wherein the compound is
41. A compound of claim 1 , wherein the compound is
42. A compound of claim 1 , wherein the compound is
43. A compound of claim 1 , wherein the compound is
44. A compound of claim 1 , wherein the compound is
45. A compound of claim 1 , wherein the compound is
46. A compound of claim 1 , wherein the compound is
47. A compound of claim 1 , wherein the compound is
48. A compound of claim 1 , wherein the compound is
49. A compound of claim 1 , wherein the compound is
50. A compound of claim 1 , wherein the compound is
51. A compound of claim 1 , wherein the compound is
52. A compound of claim 1 , wherein the compound is
53. A compound of claim 1 , wherein the compound is
54. A compound of claim 1 , wherein the compound is
55. A compound selected from the group consisting of:
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid;
{4-[3-(2-Benzooxazol-2-yl-4-bromo-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid;
{4-[2-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-ethylsulfanyl]-2-methyl-phenoxy}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-propyl-phenyl}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-chloro-phenyl}-acetic acid;
{4-[2-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-ethoxy]-phenyl}-acetic acid;
{4-[2-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-ethoxy]-3-isopropyl-phenyl}-acetic acid;
(4-{3-[4-Chloro-2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid;
{4-[3-(4-Chloro-2-phenylethynyl-phenoxy)-propoxy]-phenyl}-acetic acid;
(4-{3-[4-Chloro-2-(3-methoxy-phenylethynyl)-phenoxy]-propoxy}-phenyl)-acetic acid;
{4-[3-(4-Chloro-2-pyridin-2-ylethynyl-phenoxy)-propoxy]-phenyl}-acetic acid;
(4-{3-[4-Chloro-2-(4-methyl-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid;
{5-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-indazol-1-yl}-acetic acid;
{5-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-indol-1-yl}-acetic acid;
{5-[2-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-ethoxy]-indol-1-yl}-acetic acid;
{5-[3-(3-Benzooxazol-2-yl-phenoxy)-propoxy]-indol-1-yl}-acetic acid;
{4-[3-(3-Benzooxazol-2-yl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid;
(4-{3-[3-(4,5-Dimethyl-oxazol-2-yl)-phenoxy]-propylsulfanyl}-2-methyl-phenoxy)-acetic acid;
{1-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propyl]-1H-indol-5-yloxy}-acetic acid;
4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-chloro-benzoic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-chloro-phenoxy}-acetic acid;
3-(3-Chloro-4-{3-[2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-propionic acid;
3-(3-Chloro-4-{3-[4-chloro-2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-propionic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenoxy}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-thiophen-2-yl-phenoxy)-propoxy]-phenyl}-acetic acid;
[5-(2-Benzotriazol-2-yl-4-chloro-phenoxymethyl)-indol-1-yl]-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-methoxy-phenoxy)-propoxy]-phenyl}-acetic acid;
(4-{3-[4-Chloro-2-(4-methyl-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid ethyl ester;
{4-[3-(4-Chloro-2-phenylethynyl-phenoxy)-propoxy]-phenyl}-acetic acid ethyl ester;
(4-{3-[4-Chloro-2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid ethyl ester;
{4-[2-(2-Benzotriazol-2-yl-4-thiophen-2-yl-phenoxy)-ethoxy]-3-propyl-phenyl}-acetic acid ethyl ester;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-acetic acid methyl ester;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid ethyl ester;
{4-[3-(3-Benzooxazol-2-yl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}-acetic acid;
(4-{3-[3-(4,5-Dimethyl-oxazol-2-yl)-phenoxy]-propylsulfanyl}-2-methyl-phenoxy)-acetic acid;
(4-{3-[4-Chloro-2-(4,5-dimethyl-[1,2,3 ]triazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid;
{4-[3-(2-Benzooxazol-2-yl-4-bromo-phenoxy)-propoxy]-phenyl}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-fluoro-phenoxy)-propoxy]-phenyl}-acetic acid;
{4-[3-(2-Benzothiazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-methoxy-phenyl}-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-methoxy-acetic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-Bromo-phenyl}-acetic acid;
{3-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-acetic acid;
2-{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-2-methyl-propionic acid;
2-{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-2-methyl-phenoxy}-2-methyl-propionic acid;
2-{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-2-chloro-phenoxy}-2-methyl-propionic acid;
2-{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-propionic acid;
{4-[3-(2-Benzooxazol-2-yl-4-thiophen-2-yl-phenoxy)-propoxy]-phenyl}-acetic acid;
(4-{3-[4-Fluoro-2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid;
(4-{3-[2-(4,5,6,7-Tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-acetic acid;
4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-chloro-benzoic acid;
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-3-chloro-phenoxy}-acetic acid;
3-(3-Chloro-4-{3-[2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-propionic acid; and
3-(3-Chloro-4-{3-[4-chloro-2-(4,5,6,7-tetrahydro-benzotriazol-2-yl)-phenoxy]-propoxy}-phenyl)-propionic acid.
56. A compound selected from the group consisting of:
{4-[3-(2-Benzotriazol-2-yl-4-chloro-phenoxy)-propoxy]-phenyl}-acetic acid and {4-[3-(2-benzotriazol-2-yl-4-thiophen-2-yl-phenoxy)-propoxy]-phenyl}-acetic acid.
57. A composition comprising one or more pharmaceutically acceptable carriers, diluents or excipients and a compound of claim 1 .