2-三氟甲基喹唑啉衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of 2-Trifluoromethylquinazoline Derivatives

作　　者：吴辉 余佳[1,3] 余刚 曾晓萍[1,3] 徐广灿 孟雪玲[1,3] 徐必学[1,3] WU Hui;YU Jia;YU Gang;ZENG Xiao-ping;XU Guang-can;MENG Xue-ling;XU Bi-xue(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China;School of Pharmaceutical Sciences,Guizhou Medical University,Guiyang 550025,China;Key Laboratory of Chemistry for Natural Products of Guizhou and Chinese Academy of Sciences,Guiyang 550014,China)

机构地区：[1]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵州贵阳550014 [2]贵州医科大学药学院,贵州贵阳550025 [3]贵州省中国科学院天然产物化学重点实验室,贵州贵阳550014

出　　处：《化学试剂》2022年第5期668-673,共6页Chemical Reagents

基　　金：贵州省高层次创新型人才培养计划项目(黔科云平台人才[2016]5678);黔科合基础-ZK[2021]一般070。

摘　　要：设计合成新型2-三氟甲基喹唑啉类化合物,以期发现高效低毒的抗肿瘤活性目标分子。以2-氨基-5-硝基苯甲酸为原料,经过三氟乙酰化、环化、氯代及偶联等反应,设计合成10个2-三氟甲基喹唑啉类化合物,并通过^(1)HNMR、^(13)CNMR、^(19)FNMR进行结构确证。采用四氮唑蓝(MTT)法评价目标化合物的体外抗肿瘤活性,合成的大部分目标化合物对前列腺癌细胞(PC3、LNCaP)、人慢性髓系白血病细胞(K562)这3种癌细胞都有一定的抑制作用,其中,N-(4-甲氧基苯基)-N-甲基-2-(三氟甲基)喹唑啉-4,6-二胺的IC;分别为25.2(PC3)、515.7(LNCaP)、248.7 nmol/L(K562),该结果为2-三氟甲基喹唑啉类化合物在抗肿瘤方面的进一步研究提供参考。To discover high efficiency and low toxicity target compounds,ten novel derivatives of 2-trifluoromethylquinazoline were designed and synthesized from 2-amino-5-nitrobenzoic acid by trifluoacylation,cyclization,chlorination and coupling reaction.The structures of all target compounds were confirmed by ^(1)HNMR,^(13)CNMR,^(19)FNMR and their anti-tumor activities in vitro were demonstrated by MTT assays.Most of them had a certain inhibitory activity against prostate cancer cell lines(PC3,LNCaP),human chronic myeloid leukemia cell line(K562).The half maximal inhibitory concentration values of compound N-(4-Methoxyphenyl)-N-methyl-2-(trifluoromethyl)quinazoline-4,6-diamine against PC3,LNCaP and K562 cell lines were 25.2,515.7 and 248.7 nmol/L,respectively.The results could provide reference for further investigation of the derivatives of 2-trifluoromethylquinazoline as antitumor agents.

关 键 词：喹唑啉 三氟甲基 合成 MTT法 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]