title: Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics.
abstract: Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 antagonists that exhibit in vivo efficacy in rodent obesity models.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-0539, USA. mark.mcbriar@spcorp.com
authors.forename: Mark D
authors.initials: MD
authors.lastname: McBriar
authors.forename: Henry
authors.initials: H
authors.lastname: Guzik
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Paruchova
authors.forename: Shengjian
authors.initials: S
authors.lastname: Li
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: John W
authors.initials: JW
authors.lastname: Clader
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Brian E
authors.initials: BE
authors.lastname: Hawes
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kowalski
authors.forename: Kim
authors.initials: K
authors.lastname: O'Neill
authors.forename: Brian
authors.initials: B
authors.lastname: Spar
authors.forename: Blair
authors.initials: B
authors.lastname: Weig
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003508:Cycloheptanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D001643:Bridged Bicyclo Compounds; D003508:Cycloheptanes; D003510:Cyclohexanes; C491208:MCHR1 protein, rat; C491209:Mchr1 protein, mouse; D011979:Receptors, Pituitary Hormone; D017481:Receptors, Somatostatin; C092274:melanin-concentrating hormone receptor; D014508:Urea