Biaryl ureas as potent and orally efficacious melanin concentrating hormone receptor 1 antagonists for the treatment of obesity

被引：59

作者：

Palani, A ^{[1
]}

Shapiro, S ^{[1
]}

McBriar, MD ^{[1
]}

Clader, JW ^{[1
]}

Greenlee, WJ ^{[1
]}

Spar, B ^{[1
]}

Kowalski, TJ ^{[1
]}

Farley, C ^{[1
]}

Cook, J ^{[1
]}

van Heek, M ^{[1
]}

Weig, B ^{[1
]}

O'Neill, K ^{[1
]}

Graziano, M ^{[1
]}

Hawes, B ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 15期

关键词：

D O I：

10.1021/jm0503852

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein, we report a small molecule MCH-R1 antagonist which demonstrates oral efficacy in chronic rodent models. Substituted phenyl biaryl urea derivatives were synthesized and evaluated as MCH-R1 antagonists for the treatment of obesity. The structure-activity relationship studies in this series resulted in identification of urea 1 as a potent and selective MCH-R1 antagonist. Compound I exhibited oral efficacy in chronic (28 d) rodent models at 3-30 mpk showing significant reduction in food intake and weight gain relative to controls.

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页码：4746 / 4749

页数：4

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