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

Hiroshi Ueno, Katsuyuki Yokota, Jun Ichi Hoshi, Katsutaka Yasue, Mikio Hayashi, Itsuo Uchida, Kazuo Aisaka, Yasunori Hase, Susumu Katoh, Hidetsura Cho

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)185-189
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number1
DOIs
Publication statusPublished - 2005 Jan 3

Keywords

  • Antithrombotic effect on venous thrombosis in rats
  • Inhibition of human FXa
  • JTV-803
  • Potent and selective factor Xa (FXa) inhibitor
  • Tetrahydroisoquinoline derivatives

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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