title: Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors.
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.
authors.affiliation: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Yokota
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hoshi
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Yasue
authors.forename: Mikio
authors.initials: M
authors.lastname: Hayashi
authors.forename: Itsuo
authors.initials: I
authors.lastname: Uchida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Aisaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Hase
authors.forename: Susumu
authors.initials: S
authors.lastname: Katoh
authors.forename: Hidetsura
authors.initials: H
authors.lastname: Cho
mesh_terms: D000818:Animals; D065427:Factor Xa Inhibitors; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D044005:Tetrahydroisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D020246:Venous Thrombosis / Q000188:drug therapy / Q000201:enzymology
chemical_list: D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors; D044005:Tetrahydroisoquinolines