Benzimidazole- and benzoxazole-based inhibitors of Rho kinase

Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability.

Graphical abstractRock inhibitors have been developed based on two distinct scaffolds, benzimidazoles and benzoxazoles. SAR studies and lead optimizations are described, which resulted in novel inhibitors of ROCK-II with excellent potency and selectivity.Figure optionsDownload full-size imageDownload as PowerPoint slide