Identification Of 5h-Chromeno[3,4-C]Pyridine And 6h-Isochromeno [3,4-C] Pyridine Derivatives As Potent And Selective Dual Rock Inhibitors

A novel series of 5H-chromeno[3,4-c]pyridine, 6H-isochromeno[3,4-c]pyridine and 6H-isochromeno [4,3-d] pyrimidine derivatives as dual ROCK1 and ROCK2 inhibitors is described. Optimization led to compounds with sub-nanomolar inhibitory affinity for both kinases and excellent kinome selectivity. Compound 19 exhibited ROCK1 and ROCK2 IC50 of 0.67 nM and 0.18 nM respectively.