含1-[4-二-(4-氟苯)甲基]哌嗪官能团的1,2,3-三氮唑衍生物的合成及抗肿瘤活性研究

Synthesis and anti-tumor activity of 1,2,3-triazole bearing1-[4-bi-(4-fluorophenyl)-methyl-piperazinyl]group

以1-[二-(4-氟苯)甲基]哌嗪、苄溴、溴丙炔及NaN_3为原料,应用5 mol%的CuBr2或CuI为催化剂,DMF-H_2O为溶剂,在70℃反应4h以43~83%的收率制得了8个含有1-[4-二-(4-氟苯)甲基]哌嗪基官能团的-1,2,3-三氮唑衍生物4(a^h)。合成的8个目标化合物通过熔点测定和质谱、红外光谱、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有6个化合物对CDC25b具有较好的抑制活性,其抑制率为78~97%,IC_(50)可为16.91~11.55μM。化合物4b,4c及4g对白血病HL-60肿瘤细胞生长的抑制率分别为98%,97%和93%,IC_(50)分别为10.99μM,8.82μM和15.23μM;对肺癌A-549肿瘤细胞生长的抑制率分别可达90%,88%和73%,IC_(50)可分别达21.11μM,13.51μM和16.12μM。化合物4c对肝癌SMMC-7721细胞生长的抑制率可高达91%,IC_(50)可达16.26μM。

Eight novel 1,2,3-triazole derivatives were prepared via three steps starting from[1-bi-(4-fluorophenyl)-methyl]piperazine,benzyl bromides,propargyl bromide and sodium azide,using a very simple catalytic system composed of 5 mol%copper(II)bromide and DMF-H_2O(1∶1)as solvent at 70℃ for 4 hwith a yield(43~83%).The structures of the new compounds were characterized by IR,MS,1 H NMR,and ^(13)CNMR.The bioactive assay for the newly prepared compounds manifested that six compounds exhibited a distinct inhibitory activity against CDC25 B.Thereinto,compounds 4(b,c,g)exhibited excellent inhibitory activity against Leukemia HL-60 and Lung cancer A-549 cell(Leukemia HL-60 cell:IC_(50) value up to10.99μM,8.82μM,and 15.23μM respectively.Lung cancer A-549 cell:IC_(50) value up to 21.11μM,13.51μM and 16.26μM respectively).At the same time,compound 4 cexhibited an obvious inhibitory activity against Liver cancer SMMC-7721 cell with a IC_(50) value of 16.26μM.