The race to an orally active Factor Xa inhibitor: recent advances.
Factor Xa (fXa) is a key enzyme in the coagulation cascade and an essential component of the prothrombinase complex, which activates prothrombin to thrombin, leading to fibrin clot formation. In the search for a more effective and safer orally active anticoagulant, fXa has emerged as a major target for potential therapeutic applications in the treatment and prevention of thrombosis. This review focuses on recent advances in the chemistry of drug design and lead optimization of orally bioavailable fXa inhibitors. Many of these orally active fXa inhibitors are currently in clinical trials and are anticipated to change the landscape of thrombosis therapy.
Quan
Mimi L
ML
Bristol-Myers Squibb Co, Discovery Chemistry, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08540-5400, USA. mimi.quan@bms.com
Smallheer
Joanne M
JM
D000284:Administration, Oral; D000818:Animals; D000990:Antithrombin III / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D015394:Molecular Structure; D013923:Thromboembolism / Q000188:drug therapy
D000990:Antithrombin III