2. Academic Validation
  3. 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

  • J Med Chem. 2008 Nov 13;51(21):6631-4. doi: 10.1021/jm8005096.
Clark A Sehon 1,  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
Affiliations

Affiliation

  • 1 Departments of Medicinal Chemistry, Investigative Biology, Vascular Biology, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA. clark.a.sehon@gsk.com
PMID: 18842034 DOI: 10.1021/jm8005096
Abstract

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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