2,6-双烷氨基甲基-4-取代芳杂环氧基苯酚的合成及其抗疟活性

Synthesis and antimalarial activity of 2,6-dialkylaminomethyl-4-substituted aryloxyphenol analogues

目的合成新型杂环氨酚类抗疟药并对其活性进行研究。方法以4,7-二氯喹啉和2-甲氧基-7,10-二氯苯并[b]-1,5-萘啶为原料分别与对苯二酚单钾盐缩合得到4-取代芳氧基苯酚,再与多聚甲醛、仲胺在乙醇中发生曼尼希反应得到双曼尼希碱侧链取代的目标化合物。采用Peter′s四天抑制实验法进行两类化合物对伯氏疟原虫(Plasmodium berghei)K173株小鼠体内抗疟活性实验。结果与结论共合成了8个未见文献报道的杂环氨酚类化合物,目标化合物的结构经IR、1H-NMR光谱分析确证。初步抗疟实验表明,化合物Ⅰb,Ⅰd具有良好的抗疟活性。

Aim To design and synthesize new type of heterocyclic aminophenol analogues and evaluate their antimalarial activity. Methods 4,7-Dichloroquinoline or 2-methoxy-7, 10-dichlorobenzo [ b ]-1, 5-naphthyridine was condensed with hydroquinone monopotassium to give 4-substituted aryloxyphenol. These key intermediates were substituted with dialkylaminomethyl side chains by Mannich reaction to give target compounds. The raw material 2-methoxy-7, 10-dichlorobenzo[b]-l, 5-naphthyridine was prepared using the method reported previously. The structures were confirmed by IR, 1H-NMR spectral analysis. Their antimalarial activity against Plasmodium berghei K173 strain in mice were tested applying Peter＇s four-day oral treatment. Results and conclusion Eight unknown compounds were synthesized. Compound Ib, Id exhibit significant antimalarial activity against Plasmodium berghei.