2-(E)-(4-环戊氧基-3-甲氧基苯亚甲基)环戊酮芳胺Mannich碱类化合物的合成及抗肿瘤活性  

Synthesis and antitumor activities of 2-(E)-(4-cyclopentyloxy-3-methylbenzylidene) cyclopentanone arylamine Mannich bases

作　　者：马玉卓 尹利娜[2] 刘鹰翔[1] 梅文杰[1] 计志忠[2] 

机构地区：[1]广东药学院药物化学系,广东广州510006 [2]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2006年第3期144-149,共6页Chinese Journal of Medicinal Chemistry

基　　金：广东省自然科学基金博士启动项目(994615)

摘　　要：目的设计合成一系列2-(E)-(4-环戊氧基-3-甲氧基苯亚甲基)环戊酮Mannich碱类化合物,并对其抗肿瘤活性进行体外试验。方法以环戊酮为原料,经Stock反应、Williamson反应、Mannich反应和芳胺交换反应合成目标化合物。结果合成12个未见文献报道的新化合物,化合物的结构经1H-NMR、IR和元素分析确证。用人肝癌细胞(Bel-7402)、人口腔癌细胞(KB)进行体外抗肿瘤活性试验。初步体外活性筛选结果显示,化合物Ⅰ9具有较高的活性,对Bel-7402和KB细胞的IC50值分别为0.98、2.19μmol.L-1,但低于阳性对照药氟脲嘧啶。结论在苯亚甲基环戊酮2位侧链氨基连接的苯环的2、3、4位引入供电子基,或者在对位引入,可提高化合物活性,但在对位引入诱导效应的卤素原子,其活性下降。Aim To design and synthesize a series of 2-（ E ）-（4-cyclopentyloxy-3-methylbenzylidene） cyclopentanone arylamine Mannich bases, and to determine their antitumor activities in vitro. Methods The target compounds were synthesized by Stock enamine reaction, Williamson reaction, Mannich reaction, and arylamine exchange reaction with cyclopentanone as starting material, and their antitumor activities were assayed using human hepatic carcinoma cell line （Bel-7402）, human oral cavity epidermis squamocellular carcinoma cell line （KB）. Results Twelve compounds were obtained and they were not reported in the literature, and their chemical structures were identified by ^1H-NMR, IR and elemental analysis. Preliminary antitumor screening bioassay in vitro showed that target compound Ⅰ 9 possessed better biological activity with IC40 value 0.98 μmol·L^-1 and 2.19 μmol·L^-1 for Bel-7402 and KB carcinoma cell respectively, while lower than flurouracil （5-Fu） as postive control. Conclusion This results indicate that introduction of electron-attractive substitutes at position 2, 3 and 4, or electron-withdrawn substitutes at 4 position of amino-linked benzene ring on basic side chain of methylbenzylidenecyclopentanone contributed to the increase of anticancer activity, while introduction of halogen atoms such as chlorine and bromine with induction effect at 4 position of amino-linked benzene ring on basic side chain contributed to the decrease of the anticancer activity of target compounds.

关 键 词：药物化学 Ca合物制备 化学合成 取代苯亚甲基环戊酮Mannich碱 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]