Hit to lead account of the discovery of bisbenzamide and related ureidobenzamide inhibitors of Rho kinase

  • J Med Chem. 2010 Jan 28;53(2):759-77. doi: 10.1021/jm9014263.
Tina Morwick  1 ,  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
Affiliations
  • 1. Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06801-0368, USA. [email protected]
PMID: 20000469 DOI: 10.1021/jm9014263
Abstract

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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