| Literature DB >> 26039570 |
Jeremy Green1, Jingrong Cao1, Upul K Bandarage1, Huai Gao1, John Court1, Craig Marhefka1, Marc Jacobs1, Paul Taslimi1, David Newsome1, Tomoko Nakayama1, Sundeep Shah2, Steve Rodems2.
Abstract
The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.Entities:
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Year: 2015 PMID： 26039570 DOI： 10.1021/acs.jmedchem.5b00424
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446