Phenoxy thiazole derivatives as potent and selective acetyl-CoA carboxylase 2 inhibitors: Modulation of isozyme selectivity by incorporation of phenyl ring substituents

被引：31

作者：

Clark, Richard F. ^{[1
]}

Zhang, Tianyuan ^{[1
]}

Wang, Xiaojun ^{[1
]}

Wang, Rongqi ^{[1
]}

Zhang, Xiaolin ^{[1
]}

Camp, Heidi S. ^{[1
]}

Beutel, Bruce A. ^{[1
]}

Sham, Hing L. ^{[1
]}

Gu, Yu Gui ^{[1
]}

机构：

[1] Abbott Labs, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

acetyl-CoA carboxylase; metabolic syndrome; type-2; diabetes; obesity;

D O I：

10.1016/j.bmcl.2007.01.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A phenyl ring substitution strategy was employed to optimize the ACC2 potency and selectivity profiles of a recently discovered phenoxy thiazolyl series of acetyl-CoA carboxylase inhibitors. Ring substituents were shown to dramatically affect isozyme selectivity. Modifications that generally impart high levels of ACC2 selectivity (> 3000-fold) while maintaining excellent ACC2 potency (IC(50)s similar to 9-20 nM) were identified. (c) 2007 Elsevier Ltd. All rights reserved.

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页码：1961 / 1965

页数：5

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