Inhibitors of Factor Xa

Abstract

The development of directly acting, orally-active anticoagulants is an important drug discovery target. Many companies are involved in this area and the most popular target is Factor Xa (FXa). Inhibitors of FXa prevent the generation of thrombin which is the active enzyme in clot formation as well as platelet activation. Patents for FXa inhibitors from Aventis and AstraZeneca are reviewed here. The AstraZeneca patent is a continuation of a previous patent and contains virtually no biological data. The Aventis patent covers a large number of compounds. The compounds described have two amidino groups, which are important in many different protease inhibitors. However, this can lead to problems including lack of oral activity as well as lack of specificity. The only biological data presented are the K_ivalues for a number of compounds in an in vitro FXa assay.

• anticoagulant
• FXa
• prothrombinase