Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ) -: Synthesis and biological activity

被引：288

作者：

Sznaidman, ML

Haffner, CD

Maloney, PR

Fivush, A

Chao, E

Goreham, D

Sierra, ML

LeGrumelec, C

Xu, HE

Montana, VG

Lambert, MH

Willson, TM

Oliver, WR

Sternbach, DD

机构：

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

[2] GlaxoSmithKline, Ctr Rech, F-91951 Les Ulis, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 09期

关键词：

D O I：

10.1016/S0960-894X(03)00207-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 71 (GW0742), which shows an EC50 Of 1.1 nM against PPARdelta with 1000-fold selectivity over the other human subtypes. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1517 / 1521

页数：5

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