Desai Umesh R
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298-0540, USA.
Med Res Rev. 2004 Mar;24(2):151-81. doi: 10.1002/med.10058.
Clinically used anticoagulants are inhibitors of enzymes involved in the coagulation pathway, primarily thrombin and factor Xa. These agents can be either direct or indirect inhibitors of clotting enzymes. Heparin-based anticoagulants are indirect inhibitors that enhance the proteinase inhibitory activity of a natural anticoagulant, antithrombin. Despite its phenomenal success, current anticoagulation therapy suffers from the risk of serious bleeding. The need for safer and more effective antithrombotic agents clearly exists. The past decade has seen enormous effort directed toward discovering and/or designing new molecules with anticoagulant activity. These new molecules can be classified into (a). antithrombin and its mutants, (b). natural polysaccharides, (c). synthetic modified heparins and heparin-mimics, (d). synthetic oligosaccharides, and (e). synthetic non-sugar antithrombin activators. This review focuses on these efforts in designing or discovering new molecules that act through the antithrombin pathway of anticoagulation.
临床使用的抗凝剂是参与凝血途径的酶的抑制剂，主要是凝血酶和Xa因子。这些药物可以是凝血酶的直接抑制剂或间接抑制剂。基于肝素的抗凝剂是间接抑制剂，可增强天然抗凝剂抗凝血酶的蛋白酶抑制活性。尽管目前的抗凝治疗取得了显著成功，但仍存在严重出血的风险。显然需要更安全、更有效的抗血栓药物。在过去十年中，人们付出了巨大努力来发现和/或设计具有抗凝活性的新分子。这些新分子可分为：（a）抗凝血酶及其突变体；（b）天然多糖；（c）合成修饰肝素和肝素模拟物；（d）合成寡糖；（e）合成非糖抗凝血酶激活剂。本综述重点关注在设计或发现通过抗凝血酶抗凝途径起作用的新分子方面所做的这些努力。
