新型含三氟甲基喹唑啉衍生物的设计合成及抗肿瘤活性研究  

Design, Syntheses and Antitumor Activities of Novel Trifluoromethylquinazoline Derivatives

作　　者：韦娇梅 余佳 余刚[2,3] 曾晓萍 徐广灿[2,3] 徐必学[2,3] Wei Jiaomei;Yu Jia;Yu Gang;Zeng Xiaoping;Xu Guangcan;Xu Bixue(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang,550025;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang,550014;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang,550014)

机构地区：[1]贵州中医药大学药学院,贵阳550025 [2]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,贵阳550014 [3]贵州省中国科学院天然产物化学重点实验室,贵阳550014

出　　处：《化学通报》2022年第6期709-716,641,共9页Chemistry

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)资助。

摘　　要：为了从喹唑啉衍生物中寻找高活性的抗肿瘤分子,以2-氨基苯甲酰胺为原料,经过三氟乙酰化、环化、氯代以及偶联反应等,合成了21个2-三氟甲基喹唑啉类化合物,并通过^(1)H NMR、^(13)C NMR、^(19)F NMR进行结构确证。采用四唑盐(MTT)法评价目标化合物的体外抗肿瘤活性,结果表明,部分所合成的喹唑啉衍生物对人前列腺癌细胞(PC3、LNCaP)、人慢性髓系白血病细胞(K562)、宫颈癌细胞(Hela)以及人肺癌细胞(A549)具有抗增殖活性,其中活性较好的化合物5a和5b在5μmol/L时对LNCaP细胞增殖的抑制活性分别为61.7%、62.8%。此外N-甲基化产物5a和5b的体外抗肿瘤活性较原型化合物(4a和4b)显著提高,这为该类化合物的深入研究提供了参考依据。To find high efficiency anti-tumor target compounds from quinazoline derivatives,a series of novel 2-trifluoromethylquinazoline derivatives were synthesized starting from 2-aminobenzamide by trifluoacylation,cyclization,chlorination and coupling reaction.The chemical structures of all target compounds were characterized by ^(1)H NMR,^(13)C NMR,^(19)F NMR,and their anti-tumor activities in vitro were investigated by MTT assay method.The results indicated that some synthesized quinazoline derivatives show inhibitory effect on human prostate cancer cells(PC3 and LNCaP),chronic myelogenous leukemia cells(K562),cervical cancer cells(Hela)and human lung cancer cells(A549).Among them,compounds 5 a and 5 b have inhibitory activities of 61.7%and 62.8%on LNCaP cell proliferation at a concentration of 5μmol/L,respectively.In addition,the in vitro anti-tumor activities of the N-methylated products 5 a and 5 b are significantly higher than the corresponding prototype compounds(4 a and 4 b),which provide a basis for further research of the 2-trifluoromethylquinazoline derivatives.

关 键 词：喹唑啉 三氟甲基 合成 抗肿瘤活性 

分 类 号：TQ460.1[化学工程—制药化工]