Oral, Direct Thrombin and Factor Xa Inhibitors: The Replacement for Warfarin, Leeches, and Pig Intestines?

To prevent thromboses after surgery, patients have until now had to inject themselves daily with heparin. For stroke prophylaxis in atrial fibrillation, patients take vitamin K antagonists of the coumarin type, which have a narrow therapeutic window and whose dosage must be regularly monitored. In order to improve the standard of therapy in thromboembolic diseases such as deep‐vein thrombosis, pulmonary embolism, and stroke in atrial fibrillation, intensive research has been carried out over the last decade in the search for new, orally active thrombin and factor Xa inhibitors. A number of these compounds are already on the market or are in advanced clinical development; they could revolutionize the anticoagulant market. The race for orally available antithrombotic agents is in full swing. Several novel inhibitors of the blood‐clotting cascade have been recently introduced to the market. The new factor Xa and thrombin inhibitors (for examples see scheme) should herald a new generation of antithrombotic therapy. The history of their development is described here from the viewpoint of medicinal chemistry.