title: Cycloalkyl[b][1,4]benzodiazepinoindoles are agonists at the human 5-HT2C receptor.
abstract: Evaluation of selected compounds from our Corporate Compound Library in a human 5-HT(2C) receptor binding assay led to the discovery of WAY-629, a cyclohexyl[b][1,4]benzodiazepinoindole (K(i) 56 nM, E(max) 90%), which is selective for the 5-HT(2C) receptor versus other serotonin receptor subtypes, and dopamine, histamine, adrenergic, and muscarinic receptors. In addition, WAY-629 was active in vivo in a rat model of feeding behavior. An SAR study based on WAY-629 led to compound 11 (K(i) 13 nM, E(max) 102%).
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. sabba@wyeth.com
authors.forename: Annmarie L
authors.initials: AL
authors.lastname: Sabb
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vogel
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Welmaker
authors.forename: Joan E
authors.initials: JE
authors.lastname: Sabalski
authors.forename: Joseph
authors.initials: J
authors.lastname: Coupet
authors.forename: John
authors.initials: J
authors.lastname: Dunlop
authors.forename: Sharon
authors.initials: S
authors.lastname: Rosenzweig-Lipson
authors.forename: Boyd
authors.initials: B
authors.lastname: Harrison
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines