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

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.