Claims for Patent: 8,580,841

Summary for Patent: 8,580,841

Title:	Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders
Abstract:	The present invention relates to certain substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives of Formula (Ia):
Inventor(s):	Jones Robert M, Buzard Daniel J, Han Sangdon, Kim Sun Hee, Lehmann Juerg, Ullman Brett, Moody Jeanne V, Zhu Xiuwen, Stirn Scott
Assignee:	Arena Pharmaceuticals, Inc.
Application Number:	US13055333
Patent Claims:	2. The compound according to claim 1 , wherein n is 1.3. The compound according to claim 1 , wherein n is 2.4. The compound according to claim 1 , wherein Y is N.5. The compound according to claim 1 , wherein Y is CR.6. The compound according to claim 5 , wherein Ris H or C-Chaloalkyl.7. The compound according to claim 5 , wherein Ris H or trifluoromethyl.8. The compound according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , cyano claim 1 , C-Chaloalkoxy and C-Chaloalkyl.9. The compound according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , cyano claim 1 , trifluoromethoxy and trifluoromethyl.10. The compound according to claim 1 , wherein Ris selected from the group consisting of cyclobutyl claim 1 , cyclohexyl claim 1 , cyclopentyl claim 1 , and cyclopropyl.11. The compound according to claim 1 , wherein Z is N.12. The compound according to claim 1 , wherein Z is CR.13. The compound according to claim 12 , wherein Ris selected from the group consisting of H claim 12 , cyano claim 12 , C-Chaloalkoxy and C-Chaloalkyl.14. The compound according to claim 12 , wherein Ris selected from the group consisting of H claim 12 , cyano claim 12 , trifluoromethoxy and trifluoromethyl.15. The compound according to claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently selected from the group consisting of H claim 1 , C-Calkoxy claim 1 , C-Calkyl claim 1 , C-Calkylamino claim 1 , C-Calkylsulfonyl claim 1 , C-Calkylthio claim 1 , carboxamide claim 1 , cyano claim 1 , C-Ccycloalkoxy claim 1 , C-Ccycloalkyl claim 1 , C-Chaloalkoxy claim 1 , C-Chaloalkyl claim 1 , halogen claim 1 , heteroaryl and heterocyclyl claim 1 , wherein said C-Calkyl and C-Calkoxy are each optionally substituted with one C-Ccycloalkyl group.16. The compound according to claim 15 , wherein Ris selected from the group consisting of cyclobutyl claim 15 , cyclohexyl claim 15 , cyclopentyl claim 15 , and cyclopropyl.17. The compound according to claim 15 , wherein Ris selected from the group consisting of H claim 15 , cyano and C-Chaloalkyl.18. The compound according to claim 15 , wherein Ris selected from the group consisting of H claim 15 , cyano and trifluoromethyl.25. The compound according to claim 1 , selected from the following compounds and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclohexyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)pacetic acid;(R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;(S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;2-(7-(4-cyclopentyl-3-(trifluoromethyebenzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl) acetic acid;2-(7-(3-cyano-4-cyclohexylbenzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3yl)acetic acid;2-(7-((6-cyclopentyl-5-(trifluoromethyl)pyridin-3-yl)methoxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;2-(7-(4-cyclobutyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid; and2-(7-(4-cyclopropyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.26. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclohexyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.27. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:(R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.28. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:(S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.29. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(3-cyano-4-cyclohexylbenzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.30. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-((6-cyclopentyl-5-(trifluoromethyl)pyridin-3-yl)methoxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.31. A salt according to selected from the following salt and pharmaceutically acceptable solvates and hydrates thereof:Calcium salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.32. A salt according to selected from the following salt and pharmaceutically acceptable solvates and hydrates thereof:L-Arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.33. A hydrate according to selected from the following hydrate:D-Lysine salt of (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid hydrate.34. A solvate according to selected from the following solvate:(R)-1-Phenethylamine salt of (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid acetonitrile solvate.35. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier.36. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.37. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclobutyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.38. The compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclopropyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid.39. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclohexyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;and a pharmaceutically acceptable carrier.40. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:(R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acidand a pharmaceutically acceptable carrier.41. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:(S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;and a pharmaceutically acceptable carrier.42. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(3-cyano-4-cyclohexylbenzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;and a pharmaceutically acceptable carrier.43. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-((6-cyclopentyl-5-(trifluoromethyl)pyridin-3-yl)methoxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;and a pharmaceutically acceptable carrier.44. A pharmaceutical composition comprising a salt according to claim 1 , selected from the following salt and pharmaceutically acceptable solvates and hydrates thereof:Calcium salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acidand a pharmaceutically acceptable carrier.45. A pharmaceutical composition comprising a salt according to claim 1 , selected from the following salt and pharmaceutically acceptable solvates and hydrates thereof:L-Arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acidand a pharmaceutically acceptable carrier.46. A pharmaceutical composition comprising a hydrate according to claim 1 , selected from the following hydrate:D-Lysine salt of (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid hydrateand a pharmaceutically acceptable carrier.47. A pharmaceutical composition comprising a solvate according to selected from the following solvate:(R)-1-Phenethylamine salt of (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid acetonitrile solvateand a pharmaceutically acceptable carrier.48. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acidand a pharmaceutically acceptable carrier.49. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclobutyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acidand a pharmaceutically acceptable carrier.50. A pharmaceutical composition comprising a compound according to claim 1 , selected from the following compound and pharmaceutically acceptable salts claim 1 , solvates and hydrates thereof:2-(7-(4-cyclopropyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;and a pharmaceutically acceptable carrier.