Design and synthesis of a novel synthetic NAPAP-pentasaccharide conjugate displaying a dual antithrombotic action

Authors
Buijsman, RC Basten, JEM van Dinther, TG van der Marel, GA van Boeckel, CAA van Boom, JH
Citation
Rc. Buijsman et al., Design and synthesis of a novel synthetic NAPAP-pentasaccharide conjugate displaying a dual antithrombotic action, BIOORG MED, 9(14), 1999, pp. 2013-2018
Citations number
18
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
14
Year of publication
1999
Pages
2013 - 2018
Database
ISI
SICI code
0960-894X(19990719)9:14<2013:DASOAN>2.0.ZU;2-L
Abstract
The synthesis of a novel antithrombotic consisting of a heparin pentasaccha ride conjugated to the active site inhibitor N-(2-naphtalenesulfonyl)-glycy l-(D)-4-aminophenyl-alanyl-piperidine(NAPAP) (i.e. compound I) is reported. This conjugate shows a unique pharmacological profile both in vitro and in vivo having direct anti-thrombin and ATIII-mediated anti-Xa activity. Furt hermore, conjugate I has a prolonged in vivo half-life compared to NAPAP (1 .5 h vs 9 min.), (C) 1999 Elsevier Science Ltd. All rights reserved.