Discovery of a novel series of melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.
A new class of MCHR1 antagonists was discovered via a high-throughput screen. Optimization of the lead structure resulted in the identification of indole 10e. This compound possesses good pharmacokinetic properties across preclinical species and is efficacious in reducing food consumption in an MCH cannulated rat model and a cynomolgus monkey food consumption model.
Department of Medicinal Chemistry, Amgen, South San Francisco, CA 94080, USA. jmihalic@amgen.com
Jeffrey T
JT
Mihalic
Xiaoqi
X
Chen
Pingchen
P
Fan
Xi
X
Chen
Ying
Y
Fu
Lingming
L
Liang
Michael
M
Reed
Liang
L
Tang
Jin-Long
JL
Chen
Juan
J
Jaen
Leping
L
Li
Kang
K
Dai
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D055808:Drug Discovery; D004435:Eating / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D015394:Molecular Structure; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D007211:Indoles; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C030374:indole