哒嗪酮类化合物的合成及抑制血小板聚集作用

Synthesis of analogues of pyridazinones and its inhibition on platelet aggregation

目的 :设计合成 6 - (4-取代乙酰胺基 )苯基 - 4 ,5 -二氢 - 3(2 H ) -哒嗪酮和 6 - (4-取代乙酰胺基 )苯基 - 5 -甲基 - 4 ,5 -二氢 - 3(2 H ) -哒嗪酮两类化合物 ,以寻找作用更强、选择性更好的血小板聚集抑制剂。 方法 :以乙酰苯胺为原料 ,经傅 -克反应、满尼烯反应、水解及水合肼环合反应、酰化反应、取代反应 ,合成两类中间体及其衍生物 ,并进行体外药理实验考察其对血小板聚集的抑制作用。 结果 :共合成哒嗪酮类化合物 16个 ,其中 15个属首次报道 ,并通过元素分析和 1 H- NMR确证了它们的结构。其中化合物 (4)抑制血小板聚集的活性最强 ,比对照物 MCI- 15 4强 10倍 ;化合物 (6 )、(7)、(8)、(12 )、(13)、(14 )的活性也优于MCI- 15 4。 结论

Objective:To synthesize analogues of 6 - (4- substituted acyam inophenyl) - 4 ,5 - dihydro- 3(2 H ) pyridazinones and 6 - (4- substituted acyam inophenyl) - 5 - methyl- 4 ,5 - dihydro- 3(2 H ) pyridazinones in search for m ore potent and selective antithrombotic drugs.Methods:Many reactions such as acylation,Friedel- Crrafts reaction,hydrolysis,cyclation acylation and substitution were used to synthesize the title compounds.Born method was applied for prelim inary pharmacological test in vitro.Results:Sixteen compounds were synthesized and reported for the first time except one.Their structures were identified by element analysis and 1 H- NMR. Conclusion:Results of preliminary pharmacological test show that all synthesized com pounds have effect against platelet aggregation induced by ADP in vitro.The activity of com pound (4) is the m ost potent one.The activities of com pound (6 ) ,(7) ,(8) ,(12 ) ,(13) and (14 ) are higher than MCI- 15 4 ,respectively. [