Discovery of novel orally active ureido NPYY5 receptor antagonists

被引：16

作者：

Li, Guoqing ^{[1
]}

Stamford, Andrew W. ^{[1
]}

Huang, Ying ^{[1
]}

Cheng, Kuo-Chi ^{[3
]}

Cook, John ^{[2
]}

Farley, Constance ^{[2
]}

Gao, Jun ^{[2
]}

Ghibaudi, Lorraine ^{[2
]}

Greenlee, William J. ^{[1
]}

Guzzi, Mario ^{[2
,4
]}

van Heek, Margaret ^{[2
]}

Hwa, Joyce J. ^{[2
]}

Kelly, Joe ^{[1
]}

Mullins, Deborra ^{[4
]}

Parker, Eric M. ^{[4
]}

Wainhaus, Sam ^{[3
]}

Zhang, Xiaoping ^{[4
]}

机构：

[1] Schering Plough Res Inst, Dept Chem Res, Kenilworth, NJ 07033 USA

[2] Schering Plough Res Inst, Dept Cardiovasc & Metab Dis, Kenilworth, NJ 07033 USA

[3] Schering Plough Res Inst, Dept Exploratory Drug Metab & Pharmacokinet, Kenilworth, NJ 07033 USA

[4] Schering Plough Res Inst, Dept Neurobiol, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 03期

关键词：

neuropeptide Y; NPYY5; antagonist; obesity;

D O I：

10.1016/j.bmcl.2007.11.132

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1146 / 1150

页数：5

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