Acyclic N-(azacycloalkyl)bisindolylmaleimides:: Isozyme selective inhibitors of PKCβ

被引：91

作者：

Faul, MM ^{[1
]}

Gillig, JR

Jirousek, MR

Ballas, LM

Schotten, T

Kahl, A

Mohr, M

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Global Chem Proc Res & Dev Div, A Div, Indianapolis, IN 46285 USA

[2] Eli Lilly & Co, Lilly Res Labs, Discovery Chem Res & Technol, A Div, Indianapolis, IN 46285 USA

[3] Pfizer Global Res & Dev, La Jolla Labs, San Diego, CA USA

[4] Sphinx Labs, Res Triangle Pk, NC USA

[5] Eli Lilly & Co, Lilly Forsch, A Div, Hamburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(03)00286-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationship (SAR) trends of a new class of N-(azacycloalkyl)bisindolylmaleimides 1, acyclic derivatives of staurosporine, is described. The representative compound for this series (1e) exhibits an IC50 of 40-50 nM against the human PKCbeta(1) and PKCbeta(2) isozymes and selectively inhibits the PKCbeta isozymes in comparison to other PKC isozymes (alpha, gamma, delta, epsilon, lambda, and eta). The series is also kinase selective for PKC in comparison to other ATP-dependent kinases. A comparison of the PKC isozyme and kinase activity of the series is made to the kinase inhibitor staurosporine. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1857 / 1859

页数：3

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