Identification of a subtype selective human PPARα agonist through parallel-array synthesis

被引：169

作者：

Brown, PJ ^{[1
]}

Stuart, LW ^{[1
]}

Hurley, KP ^{[1
]}

Lewis, MC ^{[1
]}

Winegar, DA ^{[1
]}

Wilson, JG ^{[1
]}

Wilkinson, WO ^{[1
]}

Ittoop, OR ^{[1
]}

Willson, TM ^{[1
]}

机构：

[1] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 09期

关键词：

D O I：

10.1016/S0960-894X(01)00188-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using solid-phase, parallel-array synthesis, a series of urea-substituted thioisobutyric acids was synthesized and assayed for activity on the human PPAR subtypes. GW7647 (3) was identified as a potent human PPAR alpha agonist with similar to 200-fold selectivity over PPAR gamma and PPAR delta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPAR alpha in human cells and animal models of disease. (C) 2001 Elsevier Science Ltd. Ail rights reserved.

引用

页码：1225 / 1227

页数：3

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