哒嗪酮类化合物的合成及其抗血小板聚集活性  

Synthesis of pyridazinone derivatives and study of their antiplatelet aggregation activity

作　　者：章杰兵[1] 柴晓云[2] 俞世冲[2] 古卓良[1] 周国华[1] 

机构地区：[1]南京军区联勤部药品仪器检验所,南京210002 [2]第二军医大学药学院有机化学教研室,上海200433

出　　处：《第二军医大学学报》2009年第7期821-824,共4页Academic Journal of Second Military Medical University

基　　金：上海市长宁区科委科研项目(20054Y17001)~~

摘　　要：目的:研究不同取代氨基侧链的引入对哒嗪酮类化合物抗血小板聚集活性的影响。方法:以乙酰基为连接片段,引入不同的取代氨基,设计合成一系列化合物;体外药理实验参考Born方法进行。结果:设计合成了10个目标化合物,其中8个未见报道,所有化合物均经过1HNMR等确证;所有化合物都具有抗血小板聚集的活性,其中化合物(6f)、(6g)、(6h)和(6j)的抗血小板聚集活性较强,化合物(6g)和(6j)的活性是6-[4-(吡啶基-4-氨基)苯基]-4,5-二氢-3(2H)哒嗪酮(MCI-154)的5倍。结论:引入不同的取代氨基对哒嗪酮类化合物抗血小板聚集的活性有影响。Objective：To study the influence of different amino group introductions on the antiplatelet aggregation activities of pyridazinone derivatives. Methods： The target compounds were designed and synthesized by inletting different substitution amino groups using acetyl fragment as the connecting segment. Born method was used for preliminary pharmacological test in vitro. Results： Ten target compounds were designed and synthesized; 8 of them were reported firstly and all of them were confirmed by ^1HNMR spectra. The results of preliminary pharmacological test showed that all the target compounds exhibited potent antiplatelet aggregation activity. The antiaggregation activities of compounds （6f）, （6g）, （6h） and （6j） were stong; compounds （6g） and （6j） showed a 5-time higher activity than 6-[- 4-（pyridin-4-yl-amino） phenyl]-4, 5-dihydro 3 （ 2H ）- pyridazinone （MCI-154）. Conclusion： Inletting different substitution amino groups can enhance the antiplatelet aggregation activity of the compounds.

关 键 词：化学合成 哒嗪酮类 血小板聚集抑制剂 体外研究 

分 类 号：R973.2[医药卫生—药品]