title: The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT2C receptor agonist.
abstract: 5-HT2C agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT2C agonists. SAR was developed around this chemotype and compounds were identified that were potent (Ki<15 nM) and selective relative to other 5-HT2 receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats.
authors.affiliation: Athersys, Inc., 3201 Carnegie Ave., Cleveland, OH 44115, USA. brhuck@hotmail.com
authors.forename: Bayard R
authors.initials: BR
authors.lastname: Huck
authors.forename: Luis
authors.initials: L
authors.lastname: Llamas
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Robarge
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Dent
authors.forename: Jianping
authors.initials: J
authors.lastname: Song
authors.forename: William F
authors.initials: WF
authors.lastname: Hodnick
authors.forename: Chris
authors.initials: C
authors.lastname: Crumrine
authors.forename: Alain
authors.initials: A
authors.lastname: Stricker-Krongrad
authors.forename: John
authors.initials: J
authors.lastname: Harrington
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Brunden
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
mesh_terms: D000818:Animals; D004285:Dogs; D015195:Drug Design; D005247:Feeding Behavior / Q000187:drug effects; D006207:Half-Life; D009584:Nitrogen / Q000737:chemistry*; D051381:Rats; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D009584:Nitrogen