新型ADP受体拮抗剂的合成及其抗凝血活性  

Synthesis and Anticoagulant Activities of Novel ADP Receptor Antagonists

作　　者：廖上腾[1,2] 杨静[3] 刘颖[2] 于冰[2] 王平保[2] 刘登科[2] 

机构地区：[1]河南大学药学院,河南开封475000 [2]天津药物研究院天津市新药设计与发现重点实验室,天津300193 [3]天津渤海职业技术学院生物工程系,天津300408

出　　处：《合成化学》2014年第2期196-199,共4页Chinese Journal of Synthetic Chemistry

基　　金：国家"重大新药创制"科技重大专项项目(2013ZX09102014);天津市科技计划项目(09ZCKFSH01300)

摘　　要：以5,6,7,7a-四氢噻吩并[3,2-c]吡啶-2(4H)酮盐酸盐为起始原料,设计并合成了10个新型的ADP受体拮抗剂———2-乙酰氧基-5-[2-氧代-2-(4-取代哌嗪-1-基)]乙基-4,5,6,7-四氢噻吩并[3,2-c]吡啶(4a^4j),收率51%~72%,其结构经1H NMR,IR和HR-MS表征。初步生物活性测试结果表明,4a^4j均具有一定的抗凝血活性,其中4g,4i和4j的活性明显优于阳性对照药噻氯匹定,对大鼠凝血时间增长率分别为43.5%,71.8%和58.0%。Ten novel ADP receptor antagonists,2-acetoxy-5-[2-oxo-2-（4-substitutedpiperazin-1-yl）] ethyl-4,5,6,7-tetrahydro-thieno[3,2-e] pyridine（4a ～ 4j）,were designed and synthesized from 5,6,7,7a-tetrahydrothieno[3,2-c]pyridine-2（4H）-one hydrochloride in yield of 51% ～72%.The structures were characterized by 1H NMR,IR and HR-MS.Primary biological activity test indicated that 4a ～ 4j exhibited certain anti-clotting activities.4g,4i and 4j were significantly better than that of positive control drug Ticlopidine.Their growth rates of clotting time on rats were 43.5%,71.8% and 58.0%,respectively.

关 键 词：噻吩并四氢吡啶 ADP受体拮抗剂 合成 抗凝血活性 

分 类 号：O626[理学—有机化学] R914.5[理学—化学]