Novel GSK-3 inhibitors with improved cellular activity

被引：51

作者：

Peat, AJ ^{[1
]}

Garrido, D ^{[1
]}

Boucheron, JA ^{[1
]}

Schweiker, SL ^{[1
]}

Dickerson, SH ^{[1
]}

Wilson, JR ^{[1
]}

Wang, TY ^{[1
]}

Thomson, SA ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 09期

关键词：

glycogen synthase kinase-3 (GSK-3); glycogen synthesis; kinase inhibitor;

D O I：

10.1016/j.bmcl.2004.02.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of [1-(1H-benzimidazol-7-yl)-1H-pyrazolo[3,4-d] pyrimidin-4-yl] arylhydrazones was synthesized and shown to potently inhibit glycogen synthase kinase-3 (GSK-3). In light of detailed structure-activity relationships and structural knowledge of the GSK-3 binding pocket, a benzimidazole substituent was incorporated onto the pyrazolopyrimidine ccre resulting in improved potency over previous analogs. More importantly, these derivatives show low nanomolar efficacy for stimulating glycogen synthesis in vitro and therefore may be useful in the treatment of type 2 diabetes mellitus. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2127 / 2130

页数：4

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