6-取代乙酰哌嗪苯基二氢哒嗪酮类化合物的合成及其抑制血小板聚集的作用

目的：设计合成6-[4-(4-取代乙酰胺基哌嗪基)苯基]-4,5-二氢-3(2H)-哒嗪酮和6-[4-(4-取代酰胺基哌嗪基)苯基]-5-甲基-4,5-二氢-3(2H)-哒嗪酮两类化合物,寻找作用更强的血小板聚集抑制剂。方法：以乙酰苯胺为原料,经傅克反应、满尼希反应、环合反应、酰化反应合成两类中间体(M)和(N),再经缩合和取代反应得到两类目标化合物,参考Bonn方法进行体外抑制血小板聚集实验。结果：共合成目标化合物12个,其中10个属首次报道,通过元素分析,^1H-NMR确证结构。其中化合物(9)抑制血小板聚集作用的活性最强,为对照物CCI-17810的60多倍;化合物(6)、(7)、(10)、(11)、(12)的活性也优于CCI-17810．结论：目标化合物具有较强的抑制血小板聚集活性。

Synthesis of 6-substituted acylpiperazinylphenyl dihydro pyridazinones and their inhibition of platelet aggregation

Objective:To synthesize analogues of 6-[4-(4-substituted acyl piperazinyl)phenyl]-4, 5-dihydro-3(2H)pyri-dazinones and 6-[4-(4-substituted acyl piperazinyl)phenyl]-5-methyl-4,5-dihydro-3(2H)pyridazinones in search for more potent and selective antithrombotic drugs. Methods:Many reactions such as Friedel-Crafts reaction,hydrolysis,cyclation, acyla-tion,substitution were used to synthesize the title compounds. Born method was applied for preliminary pharmacological test in vitro. Results : Twelve title compounds were synthesized, in which 10 compounds were firstly reported. Their structures were identified by element analysis and 1H-NMR. Conclusion:Results of preliminary pharmacological test show that all synthesized compounds are effective against platelet aggregation induced by ADP in vitro. The activity of compound (9) is the most potent. The activity of compound (6), (7), (10), (11), (12) are also better than that of CCI-17810.