Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors

Background: A major current focus of pharmaceutical research is the develop ment of selective inhibitors of the blood coagulation enzymes thrombin or f actor Xa to be used as orally bioavailable anticoagulant drugs in thromboem bolic disorders and in the prevention of venous and arterial thrombosis. Si multaneous direct inhibition of thrombin and factor Xa by synthetic protein ase inhibitors as a novel approach to antithrombotic therapy could result i n potent anticoagulants with improved pharmacological properties.