Synthetic heparin derivatives as new anticoagulant drugs

被引：65

作者：

de Kort, M ^{[1
]}

Buijsman, RC ^{[1
]}

van Boeckel, CAA ^{[1
]}

机构：

[1] NV Organon, NL-5340 BH Oss, Netherlands

来源：

DRUG DISCOVERY TODAY | 2005年 / 10卷 / 11期

关键词：

D O I：

10.1016/S1359-6446(05)03457-4

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The journey towards a detailed mechanistic understanding of the anticoagulant action of heparin has resulted in synthetic mimetics with improved pharmacodynamic profiles. Inspired by the ternary complex formation of heparin with antithrombin III and thrombin, the active pentasaccharide fondaparinux has been succeeded by several clinical candidates, such as SR123781, that have tailor-made factor Xa and thrombin inhibitory activities combined with less aspecific binding (e.g. binding to platelet factor 4 involved in thrombocytopenia). Novel compounds with both antithrombin Ill-mediated inhibition of factor Xa and direct thrombin inhibition are emerging. Org42675 is one such compound, balancing dual inhibition of factor Xa and thrombin in one anticoagulant drug, with excellent pharmacokinetic properties and strong inhibitory activity toward clot-bound thrombin.

引用

页码：769 / 779

页数：11

共 77 条

[1] Unique overlap in the prerequisites for thrombin inhibition and oral Bioavailability resulting in potent oral antithrombotics [J].