title: Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity.
abstract: We report on the synthesis, biological evaluation and structure-activity relationships for a series of 3-benzazepine derivatives as 5-HT(2C) receptor agonists. The compounds were evaluated in functional assays measuring [3H] phosphoinositol turnover in HEK-293 cells transiently transfected with h5-HT(2C), h5-HT(2A) or h5-HT(2B) receptors. Several compounds are shown to be potent and selective 5-HT(2C) receptor agonists, which decrease food intake in a rat feeding model.
authors.affiliation: Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121-3223, USA. bsmith@arenapharm.com
authors.forename: Brian M
authors.initials: BM
authors.lastname: Smith
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Smith
authors.forename: James H
authors.initials: JH
authors.lastname: Tsai
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Schultz
authors.forename: Charles A
authors.initials: CA
authors.lastname: Gilson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Estrada
authors.forename: Rita R
authors.initials: RR
authors.lastname: Chen
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Park
authors.forename: Emily B
authors.initials: EB
authors.lastname: Prieto
authors.forename: Charlemagne S
authors.initials: CS
authors.lastname: Gallardo
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Sengupta
authors.forename: William J
authors.initials: WJ
authors.lastname: Thomsen
authors.forename: Hazel R
authors.initials: HR
authors.lastname: Saldana
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Whelan
authors.forename: Frederique
authors.initials: F
authors.lastname: Menzaghi
authors.forename: Robert R
authors.initials: RR
authors.lastname: Webb
authors.forename: Nigel R A
authors.initials: NR
authors.lastname: Beeley
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists