Factor Xa inhibitors by classical and combinatorial chemistry

• Published in: Drug discovery today Vol. 3; no. 5; pp. 223 - 231
• Main Authors: Al-Obeidi, Fahad, Ostrem, James A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.1998; Elsevier Science
• Subjects: Anticoagulants; Antithrombotic agents; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Combinatorial chemistry; Combinatorial peptide libraries; Factor Xa; Medical sciences; Pharmacology. Drug treatments; Serine protease inhibitors; Thrombosis; Serine protease inhibitors; Anticoagulants; Combinatorial peptide libraries; Combinatorial chemistry; Antithrombotic agents; Factor Xa; Thrombosis; Blood coagulation; Serine endopeptidases; Enzyme; Cardiovascular disease; Coagulation Factor Xa; Thrombin; Anticoagulant; Review; Antiplatelet agent; Vascular disease; Peptidases; Hydrolases; Chemical synthesis; Coagulation factor
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(97)01165-3

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.