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

R C Buijsman; J E Basten; T G van Dinther; G A van der Marel; C A van Boeckel; J H van Boom

doi:10.1016/s0960-894x(99)00320-0

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

Bioorg Med Chem Lett. 1999 Jul 19;9(14):2013-8. doi: 10.1016/s0960-894x(99)00320-0.

Authors

R C Buijsman¹, J E Basten, T G van Dinther, G A van der Marel, C A van Boeckel, J H van Boom

Affiliation

¹ Leiden Institute of Chemistry, Gorlaeus Laboratories, The Netherlands.

PMID: 10450972
DOI: 10.1016/s0960-894x(99)00320-0

Abstract

The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor N-(2-naphtalenesulfonyl)-glycyl-(D)-4-aminophenyl-alanyl-piperidin e (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. Furthermore, conjugate I has a prolonged in vivo half-life compared to NAPAP (1.5 h vs 9 min.).

MeSH terms

Animals
Antithrombins / chemical synthesis*
Antithrombins / pharmacology*
Carbohydrate Sequence
Dipeptides / chemistry*
Drug Design
Factor Xa Inhibitors
Half-Life
Heparin / chemistry
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Sequence Data
Oligosaccharides / chemical synthesis*
Piperidines / chemistry*
Rats
Solubility
Thrombin / antagonists & inhibitors

Substances

Antithrombins
Dipeptides
Factor Xa Inhibitors
Oligosaccharides
Piperidines
N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide
Heparin
Thrombin