Synthesis and biological activity of L-tyrosine-based PPARγ agonists with reduced molecular weight

被引：28
|
作者：
Liu, KG [1 ]
Lambert, MH
Ayscue, AH
Henke, BR
Leesnitzer, LM
Oliver, WR
Plunket, KD
Xu, HE
Sternbach, DD
Willson, TM
机构：
[1] GlaxoSmithKline, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA
[2] GlaxoSmithKline, Metab Dis Drug Discovery, Res Triangle Pk, NC 27709 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 24期
关键词：
D O I：
10.1016/S0960-894X(01)00649-7
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of PPAR gamma agonists were synthesized front L-tyrosine that incorporated low molecular weight N-substituents. The most potent analogue, pyrrole (4e), demonstrated a K-i of 6.9 nM and an EC50 of 4.7 nM in PPAR gamma binding and functional assays, respectively. Pyrrole (4e), which is readily synthesized from L-tyrosine methyl ester in four steps, also demonstrated in vivo activity in a rodent model of Type 2 diabetes. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：3111 / 3113
页数：3
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