Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists.
Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.
Kiyoi
Takao
T
Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire ML1 5SH, UK.
York
Mark
M
Francis
Stuart
S
Edwards
Darren
D
Walker
Glenn
G
Houghton
Andrea K
AK
Cottney
Jean E
JE
Baker
James
J
Adam
Julia M
JM
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D007211:Indoles; D043884:Receptor, Cannabinoid, CB1