title: Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity.
abstract: Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.
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: Bruce A
authors.initials: BA
authors.lastname: Lefker
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dombroski
authors.forename: Phoebe
authors.initials: P
authors.lastname: Chiang
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 P
authors.initials: CP
authors.lastname: Gibbons
authors.forename: Ravi
authors.initials: R
authors.lastname: Marala
authors.forename: Janice A
authors.initials: JA
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: Craig
authors.initials: C
authors.lastname: Giragossian
authors.forename: Hou
authors.initials: H
authors.lastname: Chen
authors.forename: Steven B
authors.initials: SB
authors.lastname: Coffey
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019440:Anti-Obesity Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D004285:Dogs; D004435:Eating / Q000187:drug effects; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D011392:Proline / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019440:Anti-Obesity Agents; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D011392:Proline