新型四氢吡啶并[4,3-d]嘧啶化合物的合成及生物活性

Synthesis and Biological Activity of Tetrahydropyrido[4,3-d]pyrimidine

[目的]为寻找具有较高生物活性的四氢吡啶并[4,3-d]嘧啶类农药先导化合物。[方法]以4-哌啶酮-3-羧酸乙酯盐酸盐和2,4-二氯嘧啶为初始原料,采用微波辅助技术,经3步反应,合成了16个四氢吡啶并[4,3-d]嘧啶化合物Va1~Vd4,其结构经^(1)H NMR、元素分析及高分辨质谱确证且进行杀菌活性测定。[结果]目标化合物Va4、Vb4、Vc4及Vd4的杀菌活性较好,对金黄色葡萄球菌(Staphyloccocus aureu)、大肠杆菌(Escherichia coli)的MIC值均低于对照药剂阿米卡星。[结论]目标化合物Va4、Vb4、Vc4及Vd4可作为先导化合物进一步设计合成抑菌剂。

[Aims] This study aims to find pesticide lead compounds of tetrahydropyrido[4,3-d]pyrimidine with higher active bioactivity. [Methods] 16 Tetrahydropyrido [4,3-d]pyrimidine compounds Va1-Vd4 were synthesized by using microwave assisted technology via three steps of reaction based on ethyl 4-oxopiperidine-3-carboxylate hydrochloride and 2,4-dichloropyrimidine. The structures were confirmed by ^(1)H NMR, elemental analysis and HRMS. The fungicidal activities of these compounds were also evaluated. [Results] The compounds Va4, Vb4, Vc4 and Vd4 had better bacteriostatic activity, and their MIC values for Staphyloccocus aureu and Escherichia coli were lower than that of amikacin. [Conclusions] The compounds Va4, Vb4, Vc4 and Vd4 might be considered as promising lead compounds for further design and synthesis of agricultural fungicides.