含1-[4-二(4-氟苯)甲基]哌嗪及1,2,3-三唑官能团的二硫代氨基甲酸酯的合成及抗肿瘤活性研究  

Synthesis and Anti-tumor Activity Evaluation of a Novel Series of Dithiocarbamates Bearing 1,2,3-Triazole and [1-Bi(4-fluorophenyl)methyl]piperazine Unit

作　　者：莫松[1] 丁勇[1] 张刚[1] 张震[1] 杓学蓓 李清寒[1] 杨学军[1] 陈峰[1] 

机构地区：[1]西南民族大学化学与环境保护工程学院,成都610041

出　　处：《有机化学》2017年第4期1000-1008,共9页Chinese Journal of Organic Chemistry

基　　金：四川省科技厅科技支撑计划(No.2015NZ0033);西南民族大学研究生创新基金(No.CX2016SZ063)资助项目~~

摘　　要：以1-[二(4-氟苯)甲基]哌嗪、苄溴、二硫化碳及溴丙炔为原料,应用5 mol%的Cu I为催化剂,DMF-H2O(V∶V=1∶1)为溶剂,在70℃反应4 h以34%~65%的收率制得了16个含有1-[4-二(4-氟苯)甲基哌嗪及1,2,3-三唑官能团的二硫代氨基甲酸酯衍生物.合成的16个目标化合物通过熔点测定和质谱、红外光谱、元素分析及核磁共振氢谱分析对其结构进行确证.经体外抗肿瘤活性测试表明,在20μg/m L的浓度下,有14个化合物对CDC25B具有较好的抑制活性,其抑制率高达97.96%,IC_(50)高达11.55μg/m L.在40μmol·L-1的浓度下,6个二硫代氨基甲酸酯化合物对白血病HL-60细胞生长的抑制率和IC_(50)分别可高达99.99%和12.11μg/m L,对肺癌A-549肿瘤细胞生长的抑制率和IC_(50)分别可高达93.91%和22.45μg/m L.Sixteen novel dithiocarbamates containing 1,2,3-trizaole and [1-bi（4-fluorophenyl）methyl]piperazine group were prepared via two steps starting from [1-bi（4-fluorophenyl）methyl]piperazine, propargyl bromide, methanedithione and sodium azide, using a very simple catalytic system composed of 5 mo1% copper（I） iodide and DMF-H20 （V ： V-= 1 ： l） as solvent at 70 ℃ for 4 h with moderate yield （34%~65%）. The structures of the new compounds were characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. The bioactive assay for the newly prepared compounds manifested that fourteen di- thiocarbamate derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 μg/mL （inhibitiory rate up to 97.96%, IC50 value up to 11.55 μg/mL）, and six dithiocarbamate derivatives exhibited excellent inhibitory activity against leu- kemia HL-60 and lung cancer A-549 cell in 40 prnol.L-1 （inhibitiory rate up to 99.99% and 93.91%, respectively; IC50 value up to 12.11 and 22.45 μg/mL, respectively）.

关 键 词：1-[二(4-氟苯)甲基]哌嗪 1 2 3-三唑 二硫代氨基甲酸酯 有机合成 抗肿瘤活性 

分 类 号：TQ460.1[化学工程—制药化工]