S. David Kimball Pages 441 - 468 ( 28 )
Activated thrombin plays a central role in thrombosis and hemostasis, both by controlling the coagulation process, and by activating receptors on platelets and various cell types. A safe and effective inhibitor of thrombin could be useful in the treatment of venous thrombosis, thrombosis accompanying atrial fibrillation, restenosis following angioplasty, arterial thrombosis, and in the prevention of myocardial infarction. As a result, the modulation of thrombin activity through direct, small-molecule inhibitors of the enzyme is a widely-sought goal in the pharmaceutical industry. Although several paren- teral thrombin inhibitors are currently in development, the search for small, orally bioavailable inhibitors has.proved elusive thus far. The criteria for a pharmaceutically acceptable thrombin inhibitor include high and reproducible bioavailability, selectivity, lack of toxicity, and a long duration of action. The profiles of currently studied thrombin inhibitors from peer-reviewed journals as well as from the patent literature are discussed in relation to these goals.