Benzoyl 2-methyl indoles as selective PPARγ modulators

被引：115

作者：

Acton, JJ

Black, RM

Jones, AB

Moller, DE

Colwell, L

Doebber, TW

MacNaul, KL

Berger, J

Wood, HB

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 02期

关键词：

PPAR; indole; selective PPAR modulator;

D O I：

10.1016/j.bmcl.2004.10.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Routine screening for human PPAR ligands yielded compounds 1 and 2, both of which were sub-micromolar hPPARgamma agonists. Synthetic modifications of these leads led to a series of potent substituted 3-benzyl-2-methyl indoles, a subset of which were noted to be selective PPARgamma modulators (SPPARgammaMs). SPPARgammaM 24 displayed robust anti-diabetic activity with an improved therapeutic window in comparison to a PPARgamma full agonist in a rodent efficacy model. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：357 / 362

页数：6

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