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  • Title: Active site-directed thrombin inhibitors: alpha-hydroxyacyl-prolyl-arginals. New orally active stable analogs of D-Phe-Pro-Arg-H.
    Author: Bajusz S, Barabás E, Fauszt I, Fehér A, Horváth G, Juhász A, Szabó AG, Széll E.
    Journal: Bioorg Med Chem; 1995 Aug; 3(8):1079-89. PubMed ID: 7582981.
    Abstract:
    D-alpha-Hydroxyacyl-prolyl-arginals have been designed and synthesized as orally active stable analogs of D-Phe-Pro-Arg-H, the active site-directed peptidyl thrombin inhibitor prototype. Many of the new analogs possess high in vitro anticoagulant activity while having little effect on fibrinolysis. Compounds GYKI-66104 (2), -66131 (3) and -66132 (5) effectively delay the clotting time in rabbits ex vivo and prevent thrombus formation in various thrombosis models in rabbits and rats when applied in a single oral dose of 5 mg kg-1.
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