3-(7-Azaindolyl)-4-arylmaleimides as potent, selective inhibitors of glycogen synthase kinase-3

被引：152

作者：

Zhang, HC

Ye, H

Conway, BR

Derian, CK

Addo, MF

Kuo, GH

Hecker, LR

Croll, DR

Li, J

Westover, L

Xu, JZ

Look, R

Demarest, KT

Andrade-Gordon, P

Damiano, BP

Maryanoff, BE

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, Drug Discovery, Spring House, PA 19477 USA

[2] Johnson & Johnson Res & Dev, Drug Discovery, Raritan, NJ 08869 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 12期

关键词：

GSK-3; inhibitors; kinases; azaindolylmaleimides;

D O I：

10.1016/j.bmcl.2004.03.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC50=7 and 26nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta. (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：3245 / 3250

页数：6

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