Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

被引：65

作者：

Peat, AJ ^{[1
]}

Boucheron, JA ^{[1
]}

Dickerson, SH ^{[1
]}

Garrido, D ^{[1
]}

Mills, W ^{[1
]}

Peckham, J ^{[1
]}

Preugschat, F ^{[1
]}

Smalley, T ^{[1
]}

Schweiker, SL ^{[1
]}

Wilson, JR ^{[1
]}

Wang, TY ^{[1
]}

Zhou, HQQ ^{[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;

D O I：

10.1016/j.bmcl.2004.02.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Art) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2121 / 2125

页数：5

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