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  • Title: Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors.
    Author: Ueno H, Yokota K, Hoshi J, Yasue K, Hayashi M, Uchida I, Aisaka K, Hase Y, Katoh S, Cho H.
    Journal: Bioorg Med Chem Lett; 2005 Jan 03; 15(1):185-9. PubMed ID: 15582437.
    Abstract:
    A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds 1 and 2 (JTV-803) exhibited potent inhibitory activity against FXa and good selectivity with respect to other serine proteases (thrombin, plasmin, and trypsin). In addition, compound 2 exhibited potent anti-FXa activity after intravenous and oral administration to cynomolgus monkey, and showed a dose-dependent antithrombotic effect in a rat model of venous thrombosis.
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