Discovery of novel orally active ureido NPY Y5 receptor antagonists.
We have derived a novel series of neuropeptide Y (NPY) Y5 receptor antagonists from the biphenylurea 3. Cyclohexylurea 21c, a member of the series, is a potent NPY Y5 receptor antagonist that exhibits excellent pharmacokinetic parameters in rats and dogs. On chronic oral administration to diet-induced obese rats, 21c displayed an anti-obesity profile, causing a modest reduction in food intake, a significant decrease in body weight gain, a decrease in adipose mass, and an increase in lean tissue mass.
Li
Guoqing
G
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road MS 2545, Kenilworth, NJ 07033-0359, USA. guoqing.li@spcorp.com
Stamford
Andrew W
AW
Huang
Ying
Y
Cheng
Kuo-Chi
KC
Cook
John
J
Farley
Constance
C
Gao
Jun
J
Ghibaudi
Lorraine
L
Greenlee
William J
WJ
Guzzi
Mario
M
van Heek
Margaret
M
Hwa
Joyce J
JJ
Kelly
Joe
J
Mullins
Deborra
D
Parker
Eric M
EM
Wainhaus
Sam
S
Zhang
Xiaoping
X
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004285:Dogs; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009765:Obesity / Q000139:chemically induced; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D019440:Anti-Obesity Agents; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D014508:Urea