新型2-三氟甲基-4-氨基喹啉衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activities of Novel 2-Trifluoromethyl-4-aminoquinoline Derivatives

作　　者：吕梦凡 余佳 曾晓萍[2,3] 孟雪玲[2,3] 徐广灿[2,3] 徐必学 LV Meng-fan;YU Jia;ZENG Xiao-ping;MENG Xue-ling;XU Guang-can;XU Bi-xue(College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China;State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China;The Key Laboratory of Chemistry for Natural Products of Guizhou Provincce and Chinese Academy of Sciences, Guiyang 550014, China)

机构地区：[1]贵州中医药大学,药学院,贵州贵阳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,贵州贵阳550014 [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：《合成化学》2022年第3期153-160,共8页Chinese Journal of Synthetic Chemistry

基　　金：贵州省高层次创新型人才培养计划(黔科云平台人才[2016]5678)。

摘　　要：以4-氟苯胺为起始原料,依次经环合、氯化、偶联、烷基化、还原以及亲核取代反应,设计并合成了10个新型的2-三氟甲基-4-氨基喹啉衍生物(5a~5e、6、7a~7d),其结构经^(1)H NMR、^(13)C NMR、^(19)F NMR及MS(ESI)表征。采用MTT法评价了目标化合物对前列腺癌细胞(PC3、LNCaP)和慢性髓系白血病细胞(K562)的体外抑制活性。结果表明:在5μmol·L^(-1)浓度下,化合物5b、5c及6对PC3细胞的抑制率,以及化合物7a对K562细胞的抑制率均优于阳性对照药紫杉醇,抑制率分别为50.6%、52.1%、54.7%及57.6%。Ten novel derivatives of 2-trifluoromethyl-4-aminoquinoline(5a~5e,6,7a~7d)were designed and synthesized by cyclization,chlorination,coupling,alkylation,reduction and nucleophilic substitution reactions,using 4-fluoroaniline as starting material.The structures were characterized by ^(1)H NMR,^(13)C NMR,^(19)F NMR and MS(ESI).Their anticancer activities in vitro against prostate cancer cells(PC3,LNCaP)and chronic myelogenous leukemia(K562)were demonstrated by MTT assays.The results showed that at the concentration of 5μmol·L^(-1),the inhibitory rates of compound 5b,5c and 6 on PC3 cells and compound 7a on K562 cells were better than the positive control paclitaxel,which inhibitory rates were 50.6%,52.1%,54.7%and 57.6%,respectively.

关 键 词：喹啉 三氟甲基 苯胺 合成 偶联 亲核取代 MTT法 抗肿瘤活性 

分 类 号：O62[理学—有机化学]