2,3-Diaminopyrazines as Rho kinase inhibitors

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1137-40. doi: 10.1016/j.bmcl.2009.12.012. Epub 2009 Dec 5.

Abstract

Inhibition of rho kinase (ROCK) has been recognized as an important target for a number of diseases, including glaucoma. Herein we report SAR development around two hits from a kinase library that led to the discovery of the ROCK inhibitor compound 38. In vitro and in vivo analysis of this compound, including its effects in a monkey model of glaucoma will be discussed.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Glaucoma / drug therapy
  • Glaucoma / enzymology
  • Haplorhini
  • Humans
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazines / chemistry*
  • Pyrazines / metabolism
  • Pyrazines / therapeutic use
  • Rabbits
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • Pyrazines
  • ROCK1 protein, human
  • ROCK2 protein, human
  • rho-Associated Kinases