title: Design and synthesis of orally-active and selective azaindane 5HT2c agonist for the treatment of obesity.
abstract: Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose-responsive in vivo efficacy in our pre-clinical food intake model.
authors.affiliation: Pfizer Global Research and Development, Chemistry Department, 10770 Science Center Drive, La Jolla, CA 92120, United States. kevin.k.liu@pfizer.com
authors.forename: Kevin K-C
authors.initials: KK
authors.lastname: Liu
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelius
authors.forename: Terrell A
authors.initials: TA
authors.lastname: Patterson
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Santucci
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tomlinson
authors.forename: Colleen
authors.initials: C
authors.lastname: Gibbons
authors.forename: Tristan S
authors.initials: TS
authors.lastname: Maurer
authors.forename: Ravi
authors.initials: R
authors.lastname: Marala
authors.forename: Janice
authors.initials: J
authors.lastname: Brown
authors.forename: Jimmy X
authors.initials: JX
authors.lastname: Kong
authors.forename: Eunsun
authors.initials: E
authors.lastname: Lee
authors.forename: Wendy
authors.initials: W
authors.lastname: Werner
authors.forename: Zane
authors.initials: Z
authors.lastname: Wenzel
authors.forename: Chandra
authors.initials: C
authors.lastname: Vage
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D015195:Drug Design; D000882:Haplorhini; D006801:Humans; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D001372:Aza Compounds; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists