2-substituted piperazine-derived imidazole carboxamides as potent and selective CCK1R agonists for the treatment of obesity

被引：26

作者：

Berger, Richard ^{[1
]}

Zhu, Cheng ^{[1
]}

Hansen, Alexa R. ^{[1
]}

Harper, Bart ^{[1
]}

Chen, Zhesheng ^{[4
]}

Holt, Tom G. ^{[1
]}

Hubert, James ^{[2
]}

Lee, Susan J. ^{[2
]}

Pan, Jie ^{[3
]}

Qian, Su ^{[3
]}

Reitman, Marc L. ^{[3
]}

Strack, Alison M. ^{[2
]}

Weingarth, Drew T. ^{[3
]}

Wolff, Michael ^{[1
]}

MacNeil, Douglas J. ^{[3
]}

Weber, Ann E. ^{[1
]}

Edmondson, Scott D. ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Pharmacol, Rahway, NJ 07065 USA

[3] Merck & Co Inc, Dept Metab Disorders, Rahway, NJ 07065 USA

[4] Merck & Co Inc, Dept Drug Metab & Pharmacokinet, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 17期

关键词：

cholecystokinin; CCK1R; obesity; imidazole carboxamides;

D O I：

10.1016/j.bmcl.2008.07.083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and structure-activity relationship of 1,2-diarylimidazole piperazine carboxamides bearing polar side chains as potent and selective cholecystokinin 1 receptor (CCK1R) agonists are described. Optimization of this series resulted in the discovery of isopropyl carboxamide 40, a CCK1R agonist with sub-nanomolar functional and binding activity as well as excellent potency in a mouse overnight food intake reduction assay. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4833 / 4837

页数：5

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