Thrombin inhibitors small-molecule direct

Small-molecule direct thrombin inhibitors have been structurally modified for oral administration. Approximately... 

Hursting MJ, Alford KL, Becker JC, Brooks RL, Joffrion JL, Knappenberger GD, Kogan PW, Kogan TP, McKinney A A, Schwarz RP Jr. Novastan (brand of argatroban) a small-molecule, direct thrombin inhibitor. Semin Thromb Hemost 1997 23(6) 503-16. 

Wiley, M.R. and Fisher, M.J. (1997) Small-molecule direct thrombin inhibitors. Exp. Opin. Ther. Patents 1265-1282. 

Callas D, Fareed J (1995). Comparative pharmacology of site directed antithrombin agents. Implication in drug development. Thromb. Haemostasis. 74 473-781. Hursting M J, Alford K L, Becker J P, et al. (1997). Novastan A small-molecule, direct thrombin inhibitor. Sem. Thromb. Hemostasis. 23 503-516. 

The direct thrombin inhibitors (DTIs) exert their anticoagulant effect by directly binding to the active site of thrombin, thereby inhibiting thrombin s downstream effects. This is in contrast to indirect thrombin inhibitors such as heparin and LMWH (see above), which act through antithrombin. Hirudin and bivalirudin are bivalent DTIs in that they bind at both the catalytic or active site of thrombin as well as at a substrate recognition site. Argatroban and melagatran are small molecules that bind only at the thrombin active site. 

Mattsson C, Bjorkman JA, Abrahamsson T et al. Local proCPU (TAFI) activation during thrombolytic treatment in a dog model of coronary artery thrombosis can be inhibited with a direct, small molecule thrombin inhibitor (melagatran). Thromb Haemost 2002 87 557-562. 

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