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

Journal Article (Journal Article)

The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC 50 of approximately 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.

Full Text

Duke Authors

Cited Authors

  • Feng, Y; Yin, Y; Weiser, A; Griffin, E; Cameron, MD; Lin, L; Ruiz, C; Schürer, SC; Inoue, T; Rao, PV; Schröter, T; Lograsso, P

Published Date

  • November 13, 2008

Published In

Volume / Issue

  • 51 / 21

Start / End Page

  • 6642 - 6645

PubMed ID

  • 18834107

Pubmed Central ID

  • PMC3708311

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm800986w


  • eng

Conference Location

  • United States