title: Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists.
abstract: 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.
authors.affiliation: Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire ML1 5SH, UK.
authors.forename: Takao
authors.initials: T
authors.lastname: Kiyoi
authors.forename: Mark
authors.initials: M
authors.lastname: York
authors.forename: Stuart
authors.initials: S
authors.lastname: Francis
authors.forename: Darren
authors.initials: D
authors.lastname: Edwards
authors.forename: Glenn
authors.initials: G
authors.lastname: Walker
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Houghton
authors.forename: Jean E
authors.initials: JE
authors.lastname: Cottney
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Julia M
authors.initials: JM
authors.lastname: Adam
mesh_terms: 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
chemical_list: D000577:Amides; D007211:Indoles; D043884:Receptor, Cannabinoid, CB1