The development of benzimidazoles as selective rho kinase inhibitors

E Hampton Sessions; Michael Smolinski; Bo Wang; Bozena Frackowiak; Sarwat Chowdhury; Yan Yin; Yen Ting Chen; Claudia Ruiz; Li Lin; Jennifer Pocas; Thomas Schröter; Michael D Cameron; Philip LoGrasso; Yangbo Feng; Thomas D Bannister

doi:10.1016/j.bmcl.2010.01.124

The development of benzimidazoles as selective rho kinase inhibitors

Bioorg Med Chem Lett. 2010 Mar 15;20(6):1939-43. doi: 10.1016/j.bmcl.2010.01.124. Epub 2010 Feb 1.

Authors

E Hampton Sessions¹, Michael Smolinski, Bo Wang, Bozena Frackowiak, Sarwat Chowdhury, Yan Yin, Yen Ting Chen, Claudia Ruiz, Li Lin, Jennifer Pocas, Thomas Schröter, Michael D Cameron, Philip LoGrasso, Yangbo Feng, Thomas D Bannister

Affiliation

¹ Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.

PMID: 20167489
DOI: 10.1016/j.bmcl.2010.01.124

Abstract

Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC(50)<10nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).

MeSH terms

Benzimidazoles / pharmacology*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
rho-Associated Kinases / antagonists & inhibitors*

Substances

Benzimidazoles
Protein Kinase Inhibitors
rho-Associated Kinases