- Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases.
Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases.
Journal of medicinal chemistry (2008-10-10)
Clark A Sehon, Gren Z Wang, Andrew Q Viet, Krista B Goodman, Sarah E Dowdell, Patricia A Elkins, Simon F Semus, Christopher Evans, Larry J Jolivette, Robert B Kirkpatrick, Edward Dul, Sanjay S Khandekar, Tracey Yi, Lois L Wright, Gary K Smith, David J Behm, Ross Bentley, Christopher P Doe, Erding Hu, Dennis Lee
PMID18842034
摘要
Recent studies using known Rho-associated kinase isoform 1 (ROCK1) inhibitors along with cellular and molecular biology data have revealed a pivotal role of this enzyme in many aspects of cardiovascular function. Here we report a series of ROCK1 inhibitors which were originally derived from a dihydropyrimidinone core 1. Our efforts focused on the optimization of dihydropyrimidine 2, which resulted in the identification of a series of dihydropyrimidines with improved pharmacokinetics and P450 properties.
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