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Hit to Lead Account of the Discovery of Bisbenzamide and Related Ureidobenzamide Inhibitors of Rho Kinase

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posted on 2010-01-28, 00:00 authored by Tina Morwick, Frank H. Büttner, Charles L. Cywin, Georg Dahmann, Eugene Hickey, Scott Jakes, Paul Kaplita, Mohammed A. Kashem, Steven Kerr, Stanley Kugler, Wang Mao, Daniel Marshall, Zofia Paw, Cheng-Kon Shih, Frank Wu, Erick Young
A highly selective series of bisbenzamide inhibitors of Rho-associated coiled-coil forming protein kinase (ROCK) and a related ureidobenzamide series, both identified by high throughput screening (HTS), are described. Details of the hit validation and lead generation process, including structure−activity relationship (SAR) studies, a selectivity assessment, target-independent profiling (TIP) results, and an analysis of functional activity using a rat aortic ring assay are discussed.

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