抗凝血活性分子的研究进展  

Research advances in the study of anticoagulant active molecules

作　　者：绳康佳 高妍 包涛 王嗣岑[1,2] SHENG Kang-jia;GAO Yan;BAO Tao;WANG Si-cen(School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China;Shaanxi Engineering Research Center of Cardiovascular Drugs Screening&Analysis,Xi'an 710061,China)

机构地区：[1]西安交通大学药学院,陕西西安710061 [2]陕西省心血管药物工程技术研究中心,陕西西安710061

出　　处：《药学学报》2023年第5期1103-1116,共14页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81703469,81973277)。

摘　　要：血栓诱发的心脑血管疾病的发病率在世界范围内不断增长,严重威胁人类健康。研究表明,形成血栓的三个因素分别为血流缓慢、血液高凝状态以及血管损伤。根据血栓形成的机制,抗血栓药物被分为三类,包括抗凝剂、血小板抑制剂和纤维蛋白溶解剂。由于凝血系统和抗凝血系统在血栓形成的过程中扮演着重要的作用,因此受到了越来越多的关注。目前,具有抗凝活性的新型化合物正不断涌现,一定程度上缓解了早期获批血栓治疗药物临床应用的一些问题,如出血风险高、起效慢、治疗窗口窄等。本文首先阐述了凝血机制以及血栓形成的原因和机制,然后主要总结了近年来研究报道的抗凝血活性化合物及潜在的抗血栓候选物,并对部分化合物的化学结构-药理活性关系进行了分析,以期促进开发具有抗凝血生物活性的分子,用于治疗血栓性疾病。The incidence of thrombosis-induced cardiovascular diseases is increasing worldwide and poses a serious threat to human health.Three factors,slow speed of blood flow,hypercoagulable blood and vascular damage,have been considered to be causes of thrombosis.Antithrombotic drugs have been classified into three categories based on the mechanism of thrombosis,including anticoagulants,platelet inhibitors and fibrinolytics.The coagulation and anticoagulation systems have drawn increasing attention because of the important role they play in the process of thrombosis.Novel compounds with anticoagulant activity are now emerging,alleviating to some extent some of the problems associated with the clinical use of early approved thrombotic drugs,such as high bleeding risk,slow onset of action and narrow therapeutic windows.In this review,we initially describe the mechanisms of coagulation as well as thrombosis.Meanwhile,a wide range of bioactive compounds and potential antithrombotic candidates reported in recent years have been summarized.In addition,the structure-activity relationship of certain compounds has been discussed,expecting to facilitate the development of molecules with anticoagulant biological activity for the treatment of thrombotic diseases.

关 键 词：抗凝血活性 抗血栓活性 成药性评价 小分子活性物质 构效关系 

分 类 号：R917[医药卫生—药物分析学]