含1-[4-二-(4-氟苯)甲基]哌嗪官能团的硫代酰胺的合成及生物活性

Synthesis and biological activities of thioamides bearing[1-bi-(4-fluorophenyl)methyl]-piperazine unit

以1-[二-(4-氟苯)甲基]哌嗪、端炔及单质硫为原料,应用吡啶为催化剂和溶剂,在80℃反应24h以18~84%的收率制得了17个含有1-[4-二-(4-氟苯)甲基哌嗪官能团的硫代酰胺衍生物3(a~q)。合成的17个目标化合物通过熔点测定和质谱、红外光谱及氢(碳)核磁共振谱分析对其结构进行确证。并进行了体外抗肿瘤及抗菌活性测试,测试结果表明所有化合物对大肠杆菌(E.coli)及金黄色葡萄球菌(S.aureus)的活性具有一定的抑制作用,其MIC可达64ug·mL^(-1),IC_(50)分别为42.74 ug·mL^(-1)和37.81 ug·mL^(-1);经体外抗肿瘤活性测试表明,在40uM的浓度下,化合物3(a~q)对白血病HL-60细胞及肺癌A-549肿瘤细胞的生长无抑制活性。本文合成方法具有反应操作简单和反应条件温和的优点。

Seventeen novel thioamides containing[1-bi-(4-fluorophenyl)methyl]-piperazine group were prepared via a three-component reaction involving alkynes,[1-bi-(4-fluorophenyl)methyl]-piperazine and elemental sulfur powder,using a very simple catalytic system composed of pyridine at 80℃for 24h with good yield(18~84%).The advantage was that a transition metal and an external oxidant were not needed.The structures of the new compounds 3(a~q)were characterized by IR,HMRS,^(1)H NMR,and ^(13)C NMR.The bioactive assay for the newly prepared compounds manifested that all compounds thioamides derivatives exhibited certain inhibitory activity against E.coli(MIC 64 ug·mL^(-1),IC_(50) 42.74 ug·mL^(-1))and S.aureus(MIC 64 ug·mL^(-1),IC_(50) 37.81 ug·mL^(-1)).While all thioamides derivatives had no inhibitory activity on Leukemia HL-60 and Lung cancer A-549 cell in 40uM.