新型含有1,4-苯并二噁烷骨架化合物的设计合成与ROCK2抑制活性研究

Study on Design Synthesis of Novel Skeleton Compounds Containing 1, 4-Phenyldioxane and Its ROCK2 Inhibitory Activity

ROCK2 (Rho相关卷曲螺旋蛋白激酶2)抑制剂临床上用于治疗青光眼。Netarsudil和化合物Ⅱ具有很高的ROCK2抑制活性。该实验将化合物Ⅱ的骨架进行了翻转,将活性基团与苯环相连,同时活性基团由Netarsudil的类似活性基团替代。设计并合成了化合物10a-g和13a-c,评估了这些化合物的ROCK2体外酶抑制活性。初步总结了这些化合物的构效关系,发现其中的两个化合物具有一定的ROCK2抑制活性。

ROCK2(Rho Associated Coiled-Coil Containing Protein Kinase 2) inhibitors have been used for the treatment of glaucoma. Netarsudil and compound II have high ROCK2 inhibitory activity. In this paper, the skeleton of compound II was flipped, and the active group was connected to the benzene ring. Meanwhile, the active group was replaced by the similar active group of Netarsudil. Compounds 10 a-g and 13 a-c were designed, synthesized, and evaluated by ROCK2 enzyme inhibitory activity. Preliminary structure–activity relationships for these compounds have been summarized, and two compounds were found to have certain ROCK2 inhibitory activity.