Panpan Chen, Cai Chen, Yizheng Zheng, Fangjun Chen, Zhaojun Liu, Shenhong Ren, Hangyu Song, Tongdan Liu, Zhipeng Lu, Hongbin Sun, Yi Kong, Haoliang Yuan
Patients with arterial embolic disease have benefited greatly from antiplatelet therapy. However, hemorrhage risk of antiplatelet agents cannot be ignored. Herein, we describe the discovery of 2,3-dihydro[1,4]dioxino[2,3- g ]benzofuran compounds as novel PAR4 antagonists. Notably, the isomers 36 and 37 with the chemotype of phenoxyl methylene substituted on the 2,3-dihydro-1,4-dioxine ring exhibited potent in vitro antiplatelet activity (IC50 = 26.13 nM for 36 and 14.26 nM for 37 ) and significantly improved metabolic stability in human liver microsomes ( T 1/2 = 97...
March 29, 2024: Journal of Medicinal Chemistry