Advances in the Development of Novel Factor Xa Inhibitors: A Patent Review

Development of new anticoagulants has been in constant demand throughout the world due to increasing rate of morbidity and mortality caused by thrombotic diseases. Factor Xa (FXa), one of the enzymes and validated target for anticoagulation, regulates the production of thrombin in the coagulation cascade. The importance of oral FXa inhibitors like rivaroxaban, apixaban and edoxaban in thromboembolic conditions is well supported by increasing number of patents and research publications during the recent years. Direct FXa inhibitors as antithrombotic agents offer selective, efficacious and orally active therapy with respect to the other traditional anticoagulants. Newly developed patented molecules are mainly structural bioisosteres of existing drugs and have exhibited better efficacy and safety profile. Development of antidotes for oral direct FXa inhibitors is in pipeline and their expected approval for therapeutic purposes will be further beneficial to anticoagulation therapy. This review is mainly focused on industrial and academic patents on the discovery of direct FXa inhibitors. The review covers patented compounds from December 2011 till date, describing various structural modifications along with biological activity data and advances in the process and formulation technologies of the reported FXa inhibitors. Keywords: Anticoagulant, apixaban, factor Xa inhibitor, rivaroxaban, thrombosis, VTE.