6-(4-取代乙酰氨基苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及其对血小板聚集的抑制作用

目的 设计并合成6-(4-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、氯化反应、烷基化反应等一系列反应合成目标化合物，并参考Bom方法进行体外药理实验。结果共合成6-(4-取代苯基)-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、IR确证结构。初步的体外药理实验表明：大部分目标化合物都不同程度地抑制了ADP诱导的新西兰大白兔血小板的聚集。结论11个目标化合物中化合物(8)抑制血小板聚集作用的活性最强，超过对照化合物CCI-17810，化合物(1)、(2)、(4)等也有较强的活性。

Synthesis of analogues 6-(4-substituted-phenyl)-4,5-dihydro-3(2H)-pyridazinones and study of its platelet aggregation inhibitory activity

OBJECTIVE Analogues 6-(4-substituted-phenyl)-4,5-dihydro-3(2H)-pyridazinones is synthesized for more potent and selective antithrombotic drugs.METHODS A series of reactions,such as acylation,Friedel-Crafts reaction,hydrolysis,cyclation,chlorination 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 1 HNMR.CONCLUSION Results of preliminary pharmacological tests showed that all compounds synthesized have activity against platelet aggregation induced by ADP in vitro.The activity of compound (8) is the most potent.Compound (1),(2),(4) have the potent activities too.