The coagulation factor Xa (FXa) plays a central role in the blood coagulation cascade. Recent studies have shown that FXa is a particularly attractive target for the development of oral antithrombotic agents. In view of the excellent pharmaceutical properties of 1,2-phenylenediamine-based FXa inhibitors and the reported structure-activity relationship (SAR) analysis of FXa inhibitors, we designed and synthesized a series of 3,4-diaminobenzoyl-based FXa inhibitors. Intensive SAR studies on this new series led to the discovery of 3,4-dimethoxyl substituted compound 7b. 7b is a highly potent, selective, direct FXa inhibitor with excellent in vivo antithrombotic activity.
Keywords: 3,4-Diaminobenzoyl-based FXa inhibitors; Antithrombotic agents; FXa inhibitor; Thrombosis.
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