Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics.
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.
McBriar
Mark D
MD
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-0539, USA. mark.mcbriar@spcorp.com
Guzik
Henry
H
Xu
Ruo
R
Paruchova
Jaroslava
J
Li
Shengjian
S
Palani
Anandan
A
Clader
John W
JW
Greenlee
William J
WJ
Hawes
Brian E
BE
Kowalski
Timothy J
TJ
O'Neill
Kim
K
Spar
Brian
B
Weig
Blair
B
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
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