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

摘要

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.