Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE),
myocardial infarction (MI) and ischemic strokes are mainly responsible for people’s morbidity and
mortality and have severely affected the people’s quality of life all over the world. According to WHO
statistics, an average of 17 million people are killed by the thromboembolic diseases each year globally.
Therefore, the prevention and treatment of thromboembolic diseases have received widespread attention
in recent years. Based on thrombotic mechanism, anti-thrombotic drugs are mainly divided into
anticoagulants, antiplatelet agents and direct thrombolytic drugs. In particular, anticoagulants such as vitamin K antagonists
(VKAs), unfractionated heparin (UFH), and low-molecular-weight heparins (LMWHs) have become the main therapies
for pre-treatment of thromboembolic disorders. However, the limitations of traditional anticoagulants such as slow
onset of action, dose-adjusted requirement, drug-drug and drug-food interactions have restricted their improvement in the
clinical treatment. The mechanism of the thromboembolic disorders has indicated that coagulation factor Xa (fXa) plays a
pivotal role in the blood coagulation cascade. Thus, selective inhibition of fXa by diminishing the amplified generation of
thrombin without affecting the pre-existing thrombin levels can provide better antithrombotic effect, thereby causing less
impairment of primary hemostasis. In this paper, we mainly introduce the recent advances of fXa inhibitors, with focus on
their biological activity and structure-activity relationship (SAR) information. In particular, the inspirations from the
structures of the fXa inhibitors and their future direction are highlighted.