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.
引用
收藏
页码：3245 / 3250
页数：6
相关论文
共 32 条
[31]   Macrocyclic bisindolylmaleimides as inhibitors of protein kinase C and glycogen synthase kinase-3 [J].
Zhang, HC ;
White, KB ;
Ye, H ;
McComsey, DF ;
Derian, CK ;
Addo, MF ;
Andrade-Gordon, P ;
Eckardt, AJ ;
Conway, BR ;
Westover, L ;
Xu, JZ ;
Look, R ;
Demarest, KT ;
Emanuel, S ;
Maryanoff, BE .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (18) :3049-3053
[32]  
2003, LIGANDFIT CERIUS 2 V
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