Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors

Yangbo Feng, Yan Yin, Amiee Weiser, Evelyn Griffin, Michael D. Cameron, Li Lin, Claudia Ruiz, Stephan C. Schürer, Toshihiro Inoue, P. Vasanth Rao, Thomas Schröter, Philip LoGrasso

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67 Scopus citations

Abstract

The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC50 of ∼3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacology studies showed that 5 was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.

Original languageEnglish (US)
Pages (from-to)6642-6645
Number of pages4
JournalJournal of Medicinal Chemistry
Volume51
Issue number21
DOIs
StatePublished - Nov 13 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Feng, Y., Yin, Y., Weiser, A., Griffin, E., Cameron, M. D., Lin, L., Ruiz, C., Schürer, S. C., Inoue, T., Rao, P. V., Schröter, T., & LoGrasso, P. (2008). Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. Journal of Medicinal Chemistry, 51(21), 6642-6645. https://doi.org/10.1021/jm800986w