Aleglitazar, a new, potent, and balanced dual PPARα/γ agonist for the treatment of type II diabetes

被引：97

作者：

Benardeau, Agnes ^{[1
]}

Benz, Joerg ^{[1
]}

Binggeli, Alfred ^{[1
]}

Blum, Denise ^{[1
]}

Boehringer, Markus ^{[1
]}

Grether, Uwe ^{[1
]}

Hilpert, Hans ^{[1
]}

Kuhn, Bernd ^{[1
]}

Maerki, Hans Peter ^{[1
]}

Meyer, Markus ^{[2
]}

Puentener, Kurt ^{[1
]}

Raab, Susanne ^{[1
]}

Ruf, Armin ^{[1
]}

Schlatter, Daniel ^{[1
]}

Mohr, Peter ^{[1
]}

机构：

[1] F Hoffmann La Roche Ltd, Pharma Res, CH-4070 Basel, Switzerland

[2] F Hoffmann La Roche Ltd, Pharma Dev, CH-4070 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 09期

关键词：

alpha-Alkoxypropionic acids; Nuclear hormone receptors; PPAR; X-ray crystallography; Diabetes; Dyslipidemia; ACTIVATED-RECEPTOR-GAMMA; INSULIN-RESISTANCE; NUCLEAR RECEPTORS; GLUCOSE; MODEL; ACIDS;

D O I：

10.1016/j.bmcl.2009.03.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Design, synthesis, and SAR of novel alpha-alkoxy-beta-arylpropionic acids as potent and balanced PPAR alpha gamma coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：2468 / 2473

页数：6

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