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

摘要

The invention relates to tricyclic1-[(indol-3-yl)carbonyl]piperazine derivative having the generalFormula (I) wherein X is CH2, O or S; R represents 1-3substituents independently selected from H, (C1-4)alkyl,(C1-4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 isH or (C1-4)alkyl; R3, R3', R4' R4', R5, R5' and R6' areindependently hydrogen or (C1-4)-alkyl, optionally substitutedwith (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or(C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OHor halogen; or R6 forms together with R7a 4-7 memberedsaturated heterocyclic ring, optionally containing a furtherheteroatom selected from O and S; R7 forms together withR6 a 4-7 membered saturated heterocydic ring, optionallycontaining a further heteroatom selected from O and S; orR7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionallysubstituted with OH, halogen or (C1-4)alkyloxy; or apharmaceutically acceptable salt thereof. The invention also relates topharmaceutical compositions comprising said tricyclic1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of thesederivatives in the treatment of pain, such as peri-operativepain, chronic pain neuropathic pain, cancer pain, and pain and spasticityassociated with multiple sclerosis.