Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account

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• 作者：Frank Wu ; Frank H. Bü ; ttner ; Rhonda Chen ; Eugene Hickey ; Scott Jakes ; Paul Kaplita ; Mohammed A. Kashem ; Steven Kerr ; Stanley Kugler ; Zofia Paw ; Anthony Prokopowicz ; Cheng-Kon Shih ; Roger Snow ; Eri
• 关键词：o-Kinase inhibitors
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 June 2010
• 年：2010
• 卷：20
• 期：11
• 页码：3235-3239
• 全文大小：939 K

文摘

Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vivo proof of concept for anti-hypertensive activity.