Novel Anthranilamide-Based FXa Inhibitors: Drug Design, Synthesis and Biological Evaluation

作者：Wang, Wenzhi; Yuan, Jing; Fu, Xiaoli; Meng, Fancui; Zhang, Shijun; Xu, Weiren; Xu, Yongnan^*; Huang, Changjiang^*

来源：Molecules, 2016, 21(4): 491.

DOI：10.3390/molecules21040491

• thrombosis
• FXa inhibitor
• anthranilamide-based FXa inhibitors
• docking simulation

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon these FXa inhibitors, a series of novel anthranilamide-based FXa inhibitors were designed and synthesized. According to our study, compounds 1a, 1g and 1s displayed evident FXa inhibitory activity and excellent selectivity over thrombin in in vitro inhibition activities studies. Compounds 1g and 1s also exhibited pronounced anticoagulant activities in in vitro anticoagulant activity studies.

• 出版日期2016-4
• 单位沈阳药科大学; 天津药物研究院有限公司