Synthesis and SAR of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones as MCH-1 antagonists for the treatment of obesity.
A new series of 4-aryl-1-(indazol-5-yl)pyridin-2(1H)ones possessing MCH-1 receptor antagonism is presented. Suzuki coupling of boronic acids with key triflate 6 allowed rapid generation of a range of analogs. The SAR of the MCH-1 receptor was explored with a variety of aryl and heterocyclic moieties. Selected compounds were studied in a five-day diet induced obese mouse model to evaluate their potential use as weight loss agents.
Hadden
Mark
M
AMRI, 26 Corporate Circle, Albany, NY 12212-5098, USA. mark.hadden@amriglobal.com
Deering
Dustin M
DM
Henderson
Alan J
AJ
Surman
Matthew D
MD
Luche
Michele
M
Khmelnitsky
Yuri
Y
Vickers
Steven
S
Viggers
Jean
J
Cheetham
Sharon
S
Guzzo
Peter R
PR
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D011725:Pyridines; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor