| abstract |
The present invention relates generally to agonists of cannabinoid CB1 receptors that can be used in the treatment of pain, such as intraoperative pain, chronic pain, neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis. For indole derivatives having the formula (I) or pharmaceutically acceptable salts thereof, Wherein A represents a 5-membered aromatic heterocycle, X 1 , X 2 and X 3 are independently selected from N, O, S and CH, and Y represents CH 2 , O, S or SO 2 R 1 is H, (C 1-4 ) alkyl, (C 1-4 ) alkyloxy, CN or halogen; R 2 , R 2 ′, R 3 , R 3 ′, R 4 , R 4 ′, R 5 and R 5 ′ are independently hydrogen, (C 1-4 ) alkyl (optionally substituted with OH) or CO—OR a , or the twin substituents R 3 and R 3 ′ or A pair of R 5 and R 5 ′ taken together represents a keto group, and the others are all hydrogen or (C 1-4 ) alkyl; or R 2 and R 5 taken together are methylene or represents an ethylene bridge, and R 2 ', R 3, R 3', R 4 R 4 'and R 5' is hydrogen, n is 1 or 2; (., Optionally substituted with OH) R 6 is H, (C 1-4) alkyl, (C 1-4) alkyl Oxy, CO—NR 9 R 10 , CO—OR 11 or 1,2,4-oxadiazol-3-yl), SO 2 NR 12 R 13 or COOR 14 ; R 7 is H or halogen, R 8 Is (C 1-4 ) alkyl; R 9 and R 10 are independently hydrogen, (C 1-4 ) alkyl or (C 3-7 ) cycloalkyl, where these alkyl groups are OH or Optionally substituted with (C 1-4 ) alkyloxy, R 11 is H or (C 1-4 ) alkyl; R 12 and R 13 are independently H or (C 1-4 ) alkyl Yes; R 1 4 is (C 1-6 ) alkyl. |