Claims
- 1. A compound of the formula
- 2. A compound according to claim 1, wherein Ar is
(A) phenyl or phenyl(C1-C6)alkyl, where the phenyl portion of each is optionally substituted with up to 3 groups independently selected from halogen, (C1-C6)alkyl, hydroxy, halogen, (C1-C6)haloalkyl, (C2-C6)haloacetyl, cyano, nitro, (C1-C6)alkanoyl, (C1-C6)alkylthio, (C1-C6)haloalkylthio, OR7, SR7, S(O)R7, S(O)2R7 and N(R7)2 wherein each R7 is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 haloalkoxy; or (B) a heterocyclic 5-membered ring having one nitrogen, oxygen or sulfur, two nitrogens one of which may be replaced by oxygen or sulfur, or three nitrogens one of which may be replaced by oxygen or sulfur, said heterocyclic 5-membered ring substituted by one or two fluoro, chloro, (C1-C6)alkyl or phenyl, or condensed with benzo, or substituted by one of pyridyl, furyl or thienyl, the phenyl and benzo rings being optionally substituted by
one of iodo, cyano, nitro, perfluoroethyl, trifluoroacetyl, or (C1-C6)alkanoyl, one or two of fluoro, chloro, bromo, hydroxy, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, trifluoromethoxy, trifluoromethylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl or trifluoromethyl, or two fluoro or two trifluoromethyl with one hydroxy or one (C1-C6)alkoxy, or one or, preferably, two fluoro and one trifluoromethyl, or three fluoro, said pyridyl, furyl or thienyl optionally substituted in the 3-position by fluoro, chloro, bromo, (C1-C6)alkyl or (C1-C6)alkoxy; (C) a heterocyclic 6-membered ring having one to three nitrogen atoms, or one or two nitrogen atoms and one oxygen or sulfur, said heterocyclic 6-membered ring substituted by one or two (C1-C6)alkyl or phenyl, or condensed with benzo, or substituted by one of pyridyl, furyl or thienyl, said phenyl or benzo optionally substituted by one of iodo or trifluoromethylthio, or one or two of fluoro, chloro, bromo, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, or trifluoromethyl, and said pyridyl, furyl or thienyl optionally substituted in the 3-position by fluoro, chloro, (C1-C6)alkyl or (C1-C6)alkoxy; said benzo-condensed heterocyclic 5-membered or 6-membered rings optionally substituted in the heterocyclic 5-membered or 6-membered ring by one of fluoro, chloro, bromo, methoxy, or trifluoromethyl; (D) oxazole or thiazole condensed with a 6-membered aromatic group containing one or two nitrogen atoms, with thiophene or with furane, each optionally substituted by one of fluoro, chloro, bromo, trifluoromethyl, methylthio or methylsulfinyl; (E) imidazolopyridine or triazolopyridine optionally substituted by one of trifluoromethyl, trifluoromethylthio, bromo, or (C1-C6)alkoxy, or two of fluoro or chloro; (F) thienothiophene or thienofuran optionally substituted by one of fluoro, chloro or trifluoromethyl; (G) thienotriazole optionally substituted by one of chloro or trifluoromethyl; (H) naphthothiazole; naphthoxazole; or thienoisothiazole.
- 3. A compound according to claim 1, wherein Z is (C1-C6)alkylene and Ar is a substituted phenyl of Formula II or a substituted benzothiazole of Formula III
- 4. A compound according to claim 3, wherein R8, R8′, R9, R9′, R10, R11, R12, R13 and R14 are independently hydrogen, hydroxy, (C1-C6)alkoxy, halogen, (C1-C6)alkyl, halogen, (C1-C6)haloalkyl, cyano, nitro, or N(R7)2 wherein each R7 is independently hydrogen or C1-C6 alkyl.
- 5. A compound according to claim 4, wherein R8, R8′, R9, R9′, R10, R11, R12, R13 and R14 are independently hydrogen, fluorine, chlorine, bromine, trifluoromethyl or nitro.
- 6. A compound according to claim 4, wherein Z is (C1-C3)alkylene and Ar is
- 7. A compound according to claim 6, wherein D is selected from:
- 8. A compound according to claim 7, wherein A and Z are both methylene.
- 9. A compound according to claim 8, wherein R′ is hydroxy or C1-C6 alkoxy.
- 10. A compound according to claim 9, wherein D is
- 11. A compound according to claim 9 where D is
- 12. A compound according to claim 9, wherein D is
- 13. A compound according to claim 9, where D is
- 14. A compound according to claim 13, wherein D is
- 15. A compound according to claim 6, wherein D is
- 16. A compound according to claim 15, where D is
- 17. A compound according to claim 15, where D is
- 18. A compound according to claim 15, where D is
- 19. A compound according to claim 7, wherein R11, R12, R13 and R14 are independently hydrogen, hydroxy, (C1-C2)alkoxy, trifluoromethyl, (C1-C3)alkyl, fluoro, chloro, bromo, nitro, amino, mono(C1-C2)alkylamino or di(C1-C2)alkylamino.
- 20. A compound according to claim 7, wherein R11, R12, R13 and R14 are independently hydrogen, hydroxy, fluoro, chloro, nitro, or amino.
- 21. A compound according to claim 7, wherein three of R11, R12, R13 and R14 are fluoro and the other is hydrogen.
- 22. A compound according to claim 7 where at least one of R11, R12, R13, and R14 is trifluoromethyl.
- 23. A compound according to claim 14, wherein R12 is trifluoromethyl.
- 24. A compound according to claim 10, wherein R11, R12, and R14 represent fluorine and R13 is hydrogen.
- 25. A compound according to claim 22, wherein R11, R12, and R14 represent fluorine and R13 is hydrogen.
- 26. A compound according to claim 7, wherein R′ is hydrogen.
- 27. A compound according to claims 7, wherein R′ is C1-C6 alkoxy.
- 28. A compound according to claim 1, which is
[6-Ethyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetic acid.
- 29. A compound according to claim 1, which is
[6-Methyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-l-yl]-acetic acid.
- 30. A compound according to claim 1, which is
[3-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetic acid.
- 31. A compound according to claim 1, which is
[2,6-Dimethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 32. A compound according to claim 1, which is
[2,6-Diethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 33. A compound according to claim 1, which is
[2,6-Diphenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 34. A compound according to claim 1, which is
[2,6-Dipropyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 35. A compound according to claim 1, which is
[5-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 36. A compound according to claim 1, which is
[2,4,6-Trimethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 37. A compound according to claim 1, which is
[4-Ethyl-2,6-dimethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 38. A compound according to claim 1, which is
[2-Ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 39. A compound according to claim 1, which is
[2-Benzyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 40. A compound according to claim 1, which is
[2-Phenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 41. A compound according to claim 1, which is
[6-Ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 42. A compound according to claim 1, which is
[6-Phenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 43. A compound according to claim 1, which is
[6-Benzyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 44. A compound according to claim 1, which is
[2-Phenoxy-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]-acetic acid.
- 45. A compound according to claim 1, which is
[5-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid.
- 46. A compound according to claim 1, which is
[3-Methyl-4-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid.
- 47. A compound according to claim 1, which is
[4-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid.
- 48. A compound according to claim 1, which is
[2-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid.
- 49. A compound according to claim 1, which is
[4-Methyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid.
- 50. A compound according to claim 1, which is
[5-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid.
- 51. A compound according to claim 1, which is
[2,5-Dimethyl-4-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid.
- 52. A compound according to claim 1, which is
[2-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiazol-4-yl]-acetic acid.
- 53. A method of preventing or alleviating chronic complications arising from diabetes mellitus, which comprises administering to a mammal in need of such treatment an effective amount of a compound according to claim 1.
- 54. A method according to claim 52 wherein the complications are selected from the group consisting of diabetic cataracts, retinopathy, nephropathy and neuropathy.
- 55. A method for reducing serum uric acid levels, which method comprises administering to a mammal in need of such treatment an effective amount of a compound of formula I.
- 56. A method for treating or preventing gout, which method comprises administering to a mammal an effective amount of a compound of formula I.
- 57. A pharmaceutical composition which comprises a compound of Formula I and an ACE inhibitor, together with a pharmaceutically acceptable carrier and/or diluent.
- 58. A compound of the formula:
- 59. A compound of the formula:
- 60. A compound of the formula:
- 61. A compound according to claim 59, wherein Hal is bromo.
- 62. A compound of the formula:
- 63. A compound of the formula:
- 64. A compound of the formula:
- 65. A compound according to claim [previous], wherein RC2 and RC2′ are chloro.
- 66. A compound of the formula:
- 67. A compound of the formula:
- 68. A compound of the formula:
- 69. A compound of the formula:
- 70. A compound of the formula:
- 71. A compound of the formula:
- 72. A compound according to claim previous, where RF1 and RF2 are both chloro.
- 73. A compound of the formula:
- 74. A compound of the formula:
- 75. A compound of the formula:
- 76. A compound of the formula:
- 77. A compound of the formula:
- 78. A compound according to claim 1 which is
[6-methyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetic acid (m)ethyl ester; [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]-acetic acid (m)ethyl ester; 2,6-Dimethyl-5-(4,5,7-trifluoro-benzothiazole-2-ylmethyl)-pyridin-3-yl-acetic acid hydrochloride (m)ethyl ester; [2,6-Diethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]acetic acid methyl ester; [2,6-Diphenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]acetic acid (m)ethyl ester; [2,6-Dipropyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl]acetic acid methyl ester; 5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 2,4,6-trimethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 2,6-dimethyl-4-ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 2-Ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 2-benzyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 2-phenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 6-Phenyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid (m)ethyl ester; 6-Benzyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid methyl ester; 2-phenoxy-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl)-acetic acid methyl ester; [2,5-dimethyl-4-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid (m)ethyl ester; [5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid; [4-(4,5,7-Trifluoro-benzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid methyl ester; [4-(5-trifluoromethybenzothiazol-2-ylmethyl)-thiophen-2-yl]-acetic acid (m)ethyl ester; [2-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid (m)ethyl ester; [4-methyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-thiophen-3-yl]-acetic acid methyl ester; or a pharmaceutically acceptable salt thereof.
Parent Case Info
[0001] This application claims benefit of U.S. Provisional Application Serial No. 60/336,055, filed Nov. 15, 2001, and U.S. Provisional Application Serial No. 60/378,626, filed May 7, 2002.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60336055 |
Nov 2001 |
US |
|
60378626 |
May 2002 |
US |