title: Biaryl ureas as potent and orally efficacious melanin concentrating hormone receptor 1 antagonists for the treatment of obesity.
abstract: Herein, we report a small molecule MCH-R1 antagonist which demonstrates oral efficacy in chronic rodent models. Substituted phenyl biaryl urea derivatives were synthesized and evaluated as MCH-R1 antagonists for the treatment of obesity. The structure-activity relationship studies in this series resulted in identification of urea 1 as a potent and selective MCH-R1 antagonist. Compound 1 exhibited oral efficacy in chronic (28 d) rodent models at 3-30 mpk showing significant reduction in food intake and weight gain relative to controls.
authors: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. anandan.palani@spcorp.com
authors: Anandan
authors: A
authors: Palani
authors: Sherry
authors: S
authors: Shapiro
authors: Mark D
authors: MD
authors: McBriar
authors: John W
authors: JW
authors: Clader
authors: William J
authors: WJ
authors: Greenlee
authors: Brian
authors: B
authors: Spar
authors: Timothy J
authors: TJ
authors: Kowalski
authors: Constance
authors: C
authors: Farley
authors: John
authors: J
authors: Cook
authors: Margaret
authors: M
authors: van Heek
authors: Blair
authors: B
authors: Weig
authors: Kim
authors: K
authors: O'neill
authors: Michael
authors: M
authors: Graziano
authors: Brian
authors: B
authors: Hawes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000235:genetics; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C103263:MCHR1 protein, human; C491208:MCHR1 protein, rat; D017481:Receptors, Somatostatin; D014508:Urea; D002118:Calcium