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

The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor (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.).

The synthesis of a novel antithrombotic consisting of a heparin pentasaccharide conjugated to the active site inhibitor (NAPAP) 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, the conjugate has a prolonged in vivo half-life compared to NAPAP (1.5 h vs 9 min).Figure optionsDownload full-size imageDownload as PowerPoint slide