title: Discovery of novel orally active ureido NPY Y5 receptor antagonists.
abstract: 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.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road MS 2545, Kenilworth, NJ 07033-0359, USA. guoqing.li@spcorp.com
authors.forename: Guoqing
authors.initials: G
authors.lastname: Li
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stamford
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Kuo-Chi
authors.initials: KC
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Cook
authors.forename: Constance
authors.initials: C
authors.lastname: Farley
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Lorraine
authors.initials: L
authors.lastname: Ghibaudi
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Mario
authors.initials: M
authors.lastname: Guzzi
authors.forename: Margaret
authors.initials: M
authors.lastname: van Heek
authors.forename: Joyce J
authors.initials: JJ
authors.lastname: Hwa
authors.forename: Joe
authors.initials: J
authors.lastname: Kelly
authors.forename: Deborra
authors.initials: D
authors.lastname: Mullins
authors.forename: Eric M
authors.initials: EM
authors.lastname: Parker
authors.forename: Sam
authors.initials: S
authors.lastname: Wainhaus
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D019440:Anti-Obesity Agents; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D014508:Urea