(INDOL-3-YL)-HETEROCYCLE DERIVATIVES AS AGONISTS OF THE CANNABINOID CB1 RECEPTOR

摘要

The invention relates to (indol-3-yl)-heterocycle derivatives having general Formula (I) wherein A represents a 5-membered aromatic heterocyclic ring, wherein X1, X2 and X3 are independently selected from N, O, S and CR; R is H or (C1-4)alkyl; or R, when present in X2 or X3, may form together with R3 a 5-8 membered ring; R1 is a 5-8 mem­bered saturated carbocyclic ring, optionally containing a heteroatom selected from O and S; R2 is H, CH3 or CH2-CH3; or R2 is joined together with R7 to form a 6-mem­bered ring, optionally containing a heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; R3 and R4 are independent­ly H, (C1-6)alkyl or (C3-7)cycloalkyl, the alkyl groups being optionally substituted with OH, (C1-4)alkyloxy, (C1-4)alkylthio, (C1-4)alkylsulfonyl, CN or halogen; or R3 together with R4 and the N to which they are bonded form a 4-8 membered ring optionally containing a further heteroatom selected from O and S, and which is optionally sub­stituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R5 forms a 4-8 membered ring optionally containing a further hetero­atom selected from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R, when present in X2 or X3, forms a 5-8 membered ring; R5 is H or (C1-4)alkyl; or R5 together with R3 forms a 4-8 membered ring optionally containing a further heteroatom select­ed from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyl­oxy, (C1-4) alkyloxy- (C1-4)alkyl, or halogen; R5' is H or (C1-4)alkyl; R6 represents 1-3 substituents independently selected from H, (C1-4 alkyl, (C1-4) alkyloxy, CN and halogen; R7 is H, (C1-4)alkyl, (C1-4)alkyloxy, CN or halogen; or R7 is joined together with R2 to form a 6-membered ring, optionally containing a further heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; or a pharmaceutically acceptable salt thereof, as agonists of the cannabinoid CB1 receptor, which can be used in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.