2,3-Diaminopyrazines as rho kinase inhibitors

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.

A series of 2,3-diaminopyrazines were synthesized and evaluated as rho kinase inhibitors. Compound 38 was found to have highly favorable in vitro properties, and demonstrated excellent efficacy in a monkey model of glaucoma.Figure optionsDownload as PowerPoint slide