Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors

Bioorg Med Chem Lett. 2005 Jan 3;15(1):185-9. doi: 10.1016/j.bmcl.2004.10.033.


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.

MeSH terms

  • Animals
  • Factor Xa Inhibitors*
  • Rats
  • Serine Proteinase Inhibitors / pharmacology*
  • Serine Proteinase Inhibitors / therapeutic use
  • Tetrahydroisoquinolines / pharmacology*
  • Tetrahydroisoquinolines / therapeutic use
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / enzymology


  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors
  • Tetrahydroisoquinolines