865712-37-4Relevant articles and documents
Design, synthesis, and structure-activity relationships of indole-3-heterocycles as agonists of the CB1 receptor
Morrison, Angus J.,Adam, Julia M.,Baker, James A.,Campbell, Robert A.,Clark, John K.,Cottney, Jean E.,Deehan, Maureen,Easson, Anna-Marie,Fields, Ruth,Francis, Stuart,Jeremiah, Fiona,Keddie, Neil,Kiyoi, Takao,McArthur, Duncan R.,Meyer, Karsten,Ratcliffe, Paul D.,Schulz, Jurgen,Wishart, Grant,Yoshiizumi, Kazuya
scheme or table, p. 506 - 509 (2011/02/27)
Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy
(INDOL-3-YL)-HETEROCYCLE DERIVATIVES AS AGONISTS OF THE CANNABINOID CB1 RECEPTOR
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Page/Page column 15, (2010/02/14)
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 mem-bered 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-mem-bered 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 independent-ly 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 sub-stituted 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 hetero-atom 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 select-ed from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyl-oxy, (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.
