5,6,7,8-四氢-[1,2,4]三唑并[5,1-b]喹唑啉衍生物的合成及抗肿瘤作用

Derivative synthesis and its antitumor activity of 5,6,7,8-4 H-[1,2,4]triazolo[5,1-b]quinazolines

[目的]合成5,6,7,8-四氢-[1,2,4]三唑并[5,1-b]喹唑啉衍生物,并观察其抗肿瘤作用.[方法]环己酮-2-羧酸甲酯与3-氨基-1,2,4-三唑缩合反应生成5,6,7,8-四氢-[1,2,4]三唑并[5,1-b]喹唑啉-9-醇,然后进行氯代反应得到中间体2,最后烷基化得到新型9-取代-5,6,7,8-四氢-[1,2,4]三唑并[5,1-b]喹唑啉化合物(3a^3n).化合物结构均经1 H-NMR,IR,MS确认.采用MTT比色法进行化合物抑制人体Bel-7402肝癌细胞、HCT-8结肠癌细胞及A549肺癌细胞体外活性测试.[结果]部分化合物对人体Bel-7402肝癌细胞、HCT-8结肠癌细胞及A549肺癌细胞表现出不同程度的抑制作用.其中化合物3h在5mg/L质量浓度下对A549肺癌细胞的抑制率达到82.00%.[结论]5,6,7,8-四氢-[1,2,4]三唑并[5,1-b]喹唑啉衍生物对人体肿瘤细胞表现出不同程度的抑制作用,其中化合物3h的抑制率最高.

OBJECTIVE To synthesis the derivatives of 5,6,7,8-4 H-[1,2,4]triazolo[5,1-b]quinazolines,and to study its antitumor activity.METHODS 5,6,7,8-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-9-ol was synthesized by the condensation reaction of ethyl 2-oxocyclohexane carboxylate and 1H-1,2,4-triazol-5-amine.Compound 1was treated by POCl3 to obtain intermediate 2,which was alkylated by phenols to get 9-substituted-5,6,7,8-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolines（3a-3n）.Their structures were confirmed by ^1 H-NMR,IR spectra,MS and elemental analyses.RESULTSPreliminary bioassay indicated that some compounds showed antitumor activity to human lung cancer cell line（A549）,hepatoma carcinoma cell line（Bel-7402）and colonic cancer cell line（HCT-8）in vitro by microculture tetrazolium（MTT）.The antiproliferation activity of compound 3hto A549 cells at the concentration of 5mg/L was 82.00%.CONCLUSION Quinazoline derivatives have different degree of inhibition to human tumor cells,in which the compounds 3hhas the highest inhibition rate.