The synthesis and evaluation of indolylureas as PKCα inhibitors

被引：6

作者：

Djung, Jane F. ^{[2
]}

Mears, Richard. J. ^{[1
]}

Montalbetti, Christian A. G. N. ^{[1
]}

Coulter, Thomas S. ^{[1
]}

Golebiowski, Adam ^{[2
]}

Carr, Andrew N. ^{[2
]}

Barker, Oliver ^{[1
]}

Greis, Kenneth D. ^{[2
]}

Zhou, Songtao ^{[2
]}

Dolan, Elizabeth ^{[2
]}

Davis, Gregory F. ^{[2
]}

机构：

[1] Evotec, Abingdon OX14 4SA, Oxon, England

[2] Procter & Gamble Pharmaceut Inc, Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 08期

关键词：

Protein kinase C alpha; Kinase inhibitor; Heart disease; Indolylurea; PROTEIN-KINASE-C; MOLECULAR-FORCE FIELD; CARDIAC CONTRACTILITY; HEART-FAILURE; POTENT; DESIGN; THETA; DISEASE; BINDING; GEOMETRIES;

D O I：

10.1016/j.bmc.2011.02.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PKC alpha and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKC alpha, but not PKA, are potential therapeutic targets for the treatment of heart disease. The synthesis of indolylureas are described, and a compound displaying nanomolar inhibition towards PKC alpha with significant selectivity over PKA has been identified. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2742 / 2750

页数：9

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