The synthesis and evaluation of indolylureas as PKCα inhibitors

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• 作者：Jane F. Djung^a ; Richard. J. Mears^b ; ^{richard.mears@evotec.com} ; Christian A.G.N. Montalbetti^b ; Thomas S. Coulter^b ; Adam Golebiowski^a ; ^† ; ; Andrew N. Carr^a ; Oliver Barker^b ; Kenneth D. Greis^a ; ^‡ ; ; Songtao Zhou^a ; ^§ ; ; Elizabeth Dolan^a ; Gregory F. Davis^a
• 关键词：Protein kinase C alpha ; Kinase inhibitor ; Heart disease ; Indolylurea
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：15 April 2011
• 年：2011
• 卷：19
• 期：8
• 页码：2742-2750
• 全文大小：901 K

文摘

PKCα and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKCα, 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 PKCα with significant selectivity over PKA has been identified.