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

被引：287
|
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
收藏
页码：1517 / 1521
页数：5
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