2,4-二取代-6-氯三氮唑类化合物的合成及其抗肺癌活性研究  

Synthesis and Evaluation of Anti-Lung Cancer Activity for 2,4-Disubstituted 6-Chlorotriazole Compounds

作　　者：曾宪霞 黄怀征 凌珍 张洁 谭凯丽 石欣武 何林洪 ZENG Xian-xia;HUANG Huai-zheng;LING Zhen;ZHANG Jie;TAN Kai-li;SHI Xin-wu;HE Lin-hong(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《化学试剂》2023年第8期65-71,共7页Chemical Reagents

基　　金：广西自然科学基金青年基金项目(2021GXNSFBA-075028,2023GXNSFAA026343);国家自然科学基金青年基金项目(82260673);大学生创新创业项目(8202210598137)。

摘　　要：为寻找具有抗肺癌活性的先导化合物,以2,4,6-三氯-1,3,5-三嗪为起始原料通过2~4步反应合成一系列2,4-二取代-6-氯三氮唑衍生物,结构由NMR和MS鉴定。体外细胞抗肺癌活性研究表明,多个化合物(T3、T10、T14、T15和T16)对受测细胞株表现良好的抗增殖活性,尤其是对突变型细胞株PC9、HCC827和H1975。其中,N2-([1,1′-联苯]-4-基)-6-氯-N4-(3-硝基苯基)-1,3,5-三嗪-2,4-二胺的抗增殖活性最强,所有IC50值均小于10μmol/L。尽管该化合物因为亲脂性过高难以进入后续研究,但其可作为先导化合物为该类结构衍生物的开发提供一定的指导意义。A series of 2,4-disubstituted 6-chlorotriazole derivatives were synthesized from the raw material of cyanuric chloride through two to four steps in order to find lead compounds owing anti-lung cancer activities.All the compound were identified by NMR and MS.Results of anti-lung cancer activities in vitro demonstrated that several compounds(T3,T10,T14,T15 and T16)displayed favourable anti-proliferative activities against all the cells lines in assay,especially for the cell lines with mutation including PC9,HCC817 and H1975.Among them,compound T10 revealed the best anti-proliferative activity,whose IC 50 values were all less than 10μmol/L.Although the lipophicity of this compound was so high that it could not been carried out further study,it could be used as the lead compound to provide guidance for the development of such structural derivatives.

关 键 词：2-氯-4 6-二取代三氮唑 肺癌 表皮生长因子受体 野生型 突变型 

分 类 号：R914[医药卫生—药物化学]