New thrombin inhibitors in cardiovascular disease

Thrombin is a multifunctional serine protease that plays a primary role in the pathogenic pathway of thrombosis as a consequence of its actions on the two principal components of blood clots, fibrin and activated platelets. Deficiencies in available therapies, heparin and coumadin, have recently led to an intense effort in several pharmaceutical companies to develop potent, selective, and preferably orally bioavailable direct thrombin inhibitors. Substantial progress has been made on potent and selective compounds and work is ongoing to improve other pharmacokinetic properties such as oral bioavailability and duration of action, properties necessary for successful clinical development.