Design, synthesis and biological evaluation of anthranilamide derivatives as potential factor Xa (fXa) inhibitors.
Basic Information
ID: ALA4382223
Journal: Bioorg Med Chem
Title: Design, synthesis and biological evaluation of anthranilamide derivatives as potential factor Xa (fXa) inhibitors.
Authors: Xing J, Yang L, Zhou J, Zhang H.
Abstract: Factor Xa (fXa) is a crucial player in various thromboembolic disorders. Inhibition of fXa can provide safe and effective antithrombotic effects. In this study, a series of anthranilamide compounds were designed by utilizing structure-based design strategies. Optimization at P1 and P4 groups led to the discovery of compound 16g: a highly potent, selective fXa inhibitor with pronounced in vitro anticoagulant activity. Moreover, 16g also displayed excellent in vivo antithrombotic activity in the rat venous thrombosis (VT) and arteriovenous shunt (AV-SHUNT) models. The bleeding risk evaluation showed that 16g had a safer profile than that of betrixaban at 1 mg/kg and 5 mg/kg dose. Additionally, 16g also exhibited satisfactory PK profiles. Eventually, 16g was selected to investigate its effect on hypoxia-reoxygenation- induced H9C2 cell viability. MTT results showed that H9C2 cell viability can be remarkably alleviated by 16g.
CiteXplore: 30446438
DOI: 10.1016/j.bmc.2018.09.012
Patent ID: ┄