TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS

摘要

The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1- 4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 is H or (C1-4)alkyl; R3, R3~, R4~ R4~, R5, R5~ and R6~ are independently hydrogen or (C1-4)-alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; or R 6 forms together with R7a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together wit h R6 a 4-7 membered saturated heterocydic ring, optionally containing a furthe r heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalky l, the alkyl groups being optionally substituted with OH, halogen or (C1- 4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention als o relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3 - yl)carbonyl]piperazine derivatives, and to the use of these derivatives in t he treatment of pain, such as peri-operative pain, chronic pain neuropathic pai n, cancer pain, and pain and spasticity associated with multiple sclerosis.