Peer-reviewed veterinary case report
Design, synthesis and biological evaluation of anthranilamide derivatives as potential factor Xa (fXa) inhibitors.
- Journal:
- Bioorganic & medicinal chemistry
- Year:
- 2018
- Authors:
- Xing, Junhao et al.
- Affiliation:
- Department of Organic Chemistry · China
- Species:
- rodent
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.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/30446438/