6-[4-[4-(取代苯乙酮基)哌嗪基]苯基]哒嗪酮类化合物的合成及抑制血小板聚集作用

目的：设计合成一类６－（取代苯基）－４，５－二氢－３－（２Ｈ）哒嗪酮类化合物，以期发现作用更强的血小板聚集抑制剂。方法：以乙酰苯胺为原料，经酰化反应、傅－克反应、水解反应及水合肼环合反应、溴化反应、烷基化反应等一系列反应合成目标化合物，并参考Ｂｏｒｎ方法进行体外药理实验。结果：共合成６－「４－（取代哌嗪基）苯基」－４，５－二氢－３（２Ｈ）哒嗪酮类化合物１１个，均属首次报道，并通过元素分析、＾１ＨＮＭＲ确证结构。初步的体外药理实验表明：大部分目标化合物都有不同程度的抑制ＡＤＰ诱导的新西兰大白兔血小板聚集的作用。结论：首次合成了１１个６「４－「４－（取代苯乙酮基）哌嗪基」苯基」－４，５－二氢－３（２Ｈ）哒嗪酮类化合物，其中化合物（４）抑制抑制血小板聚集作用的活性最强，与先导化合物ＣＣＩ１７８１０相当，化合物（３），

Synthesis of analogues of 6-[4-(4-substituted-piperazine)phenyl]- 4,5-di hydro-3(2H)pyridazinones and its platelet aggregation inhibitory activity

Objective: Analogues of 6 4 (4 substituted piperazine)phenyl] 4,5 dihydro 3 (2 H )pyridazinones is synthesized in search for more potent and selective antithrombotic drugs. Methods: Many reactions such as acylation, Friedel Crafts reaction, hydrolysis, cyclation,bromination and alkylation were used to synthesize the title compounds. Born method was applied for preliminary pharmacological test in vitro . Results: Eleven new compounds were synthesized. All compounds were firstly reported. Their structure were identified by element analysis and 1HNMR. Conclusion: Results of preliminary pharmacological tests show that all compounds synthesized have activity against platelet aggregation induced by ADP in vitro . The activity of compound (4) is the most potent.Compound (3),(9),(11) have the potent activities too.