Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists.
Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model.
Wu
Wen-Lian
WL
Schering Plough Research Institute, 2015 Galloping Hill Road, MS 2800, Kenilworth, NJ 07033-0539, USA. wen-lian.wu@spcorp.com
Burnett
Duane A
DA
Caplen
Mary Ann
MA
Domalski
Martin S
MS
Bennett
Chad
C
Greenlee
William J
WJ
Hawes
Brian E
BE
O'Neill
Kim
K
Weig
Blair
B
Weston
Daniel
D
Spar
Brian
B
Kowalski
Timothy
T
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects*; D004195:Disease Models, Animal; D015195:Drug Design; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D001562:Benzimidazoles; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor