| Literature DB >> 17201404 |
Robert A Stavenger1, Haifeng Cui, Sarah E Dowdell, Robert G Franz, Dimitri E Gaitanopoulos, Krista B Goodman, Mark A Hilfiker, Robert L Ivy, Jack D Leber, Joseph P Marino, Hye-Ja Oh, Andrew Q Viet, Weiwei Xu, Guosen Ye, Daohua Zhang, Yongdong Zhao, Larry J Jolivette, Martha S Head, Simon F Semus, Patricia A Elkins, Robert B Kirkpatrick, Edward Dul, Sanjay S Khandekar, Tracey Yi, David K Jung, Lois L Wright, Gary K Smith, David J Behm, Christopher P Doe, Ross Bentley, Zunxuan X Chen, Erding Hu, Dennis Lee.
Abstract
The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.Entities:
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Year: 2007 PMID： 17201404 DOI： 10.1021/jm060873p
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446