James Ostrem

Factor Xa inhibitors by classical and combinatorial chemistry

Abstract A high-priority goal in the search for new antithrombotic agents is the identification of small-molecule compounds that selectively inhibit the blood coagulation Factor Xa. These compounds should limit blood loss while controlling thrombosis following surgery, heart attacks, infection by Gram-negative organisms, and other coagulation disorders. Three naturally occurring small proteins (antistasin, tick anticoagulant peptide and yagin) and a diverse collection of small-molecule inhibitors of Factor Xa, originating from both structure-based design and screening of historical compounds and combinatorial libraries, have been described. This review summarizes recent entries into preclinical research, including a series of unique Factor Xa inhibitors recently uncovered in combinatorial peptide libraries.