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

doi:10.1016/j.bmcl.2004.10.033

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

PHA - Molecular Pharmaceutical Science

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	185-189
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2004.10.033
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2004.10.033

Cite this

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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.",

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doi = "10.1016/j.bmcl.2004.10.033",

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T1 - Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors

AU - Ueno, Hiroshi

AU - Yokota, Katsuyuki

AU - Hoshi, Jun Ichi

AU - Yasue, Katsutaka

AU - Hayashi, Mikio

AU - Uchida, Itsuo

AU - Aisaka, Kazuo

AU - Hase, Yasunori

AU - Katoh, Susumu

AU - Cho, Hidetsura

PY - 2005/1/3

Y1 - 2005/1/3

N2 - 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.

AB - 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.

KW - Antithrombotic effect on venous thrombosis in rats

KW - Inhibition of human FXa

KW - JTV-803

KW - Potent and selective factor Xa (FXa) inhibitor

KW - Tetrahydroisoquinoline derivatives

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JO - Bioorganic and Medicinal Chemistry Letters

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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