Anticoagulants

Abstract Although blood circulation is highly regulated, dysfunctional activities resulting from either deficient or excessive coagulation have serious health consequences. Insufficient clotting can lead to prolonged bleeding and hemophilia‐related conditions. Over activation of coagulation can lead to thrombosis‐related disorders, such as deep venous thrombosis, pulmonary embolism, and stroke, which together are a major cause of morbidity and mortality. Studies of the biological pathways leading to coagulation, and the resultant development and refinement of the coagulation cascade, have identified many potential biological targets for therapeutic intervention. The major challenge regarding the treatment and prevention of thromboembolic diseases is the requirement for effective anticoagulant therapy without exposing patients to an increased risk of bleeding. Preclinical and clinical evaluations of anticoagulant agents highlight this efficacy/bleeding dichotomy. This article presents the medicinal chemistry efforts leading to the discovery of inhibitors of the coagulation cascade, resulting in marketed thrombin and Factor Xa inhibitors. Also reported is the progress toward identifying emerging anticoagulants.