The Rho-associated protein kinases (ROCKs) are associated with the pathology of glaucoma and discovery of ROCK inhibitors has attracted much attention in recent years. Herein, we report a series of 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies led to the discovery of compound 12b, which showed potent activities against ROCK I and ROCK Ⅱ with IC₅₀ values of 93 nM and 3 nM, respectively. 12b also displayed considerable selectivity for ROCKs. The mean IOP-lowering effect of 12b in an ocular normotensive model was 34.3%, and no obvious hyperemia was observed. Overall, this study provides a good starting point for ROCK-targeting drug discovery against glaucoma.

Rho 相关蛋白激酶 (ROCK) 与青光眼的病理学相关，近年来 ROCK 抑制剂的发现引起了广泛关注。在此，我们报告了一系列 3,4-二氢苯并[ f ][1,4] oxazep​​in-5(2 H )-one 衍生物作为一类新的 ROCK 抑制剂。构效关系研究导致了化合物12b的发现，该化合物对 ROCK I 和 ROCK Ⅱ具有强活性，IC ₅₀值分别为 93 nM 和 3 nM。12b还显示出对 ROCK 的相当大的选择性。12b的平均眼压降低效果在眼压正常模型中为 34.3%，未观察到明显的充血。总的来说，这项研究为针对青光眼的 ROCK 靶向药物发现提供了一个很好的起点。