【作者】 郑仙明；

【导师】 胡惟孝；

【作者基本信息】 浙江工业大学 ， 生物化工， 2007， 硕士

【摘要】 抗癌药物的研究具有重要的理论意义和应用前景。本论文研究2-腈基-3-取代苯基丙烯酸类化合物的合成及其生物活性。首先发展了用DCC偶联法用腈代乙酸与胺类化合物合成腈代乙酰胺的新方法，共合成10种化合物，收率51-90％操作简便，收率较高是一种较好的合成方法应用克脑文盖尔（Knovevenagel）缩合，由五种取代苯甲醛与腈代乙酸（酯）合成了5种2-腈基-3-取代苯基丙稀酸（酯），收率43.1-95％。由取代苯甲醛与腈代乙酰胺合成了10种2-腈基-3-取代苯基丙稀酰胺，收率42-95％。其中四种为新化合物。其结构由IR、MS、NMR、及元素分析表征。一种酰胺（zxm-12）的构型通过x-光单晶衍射法测之为E式。所合成的化合物均测定了抗乙酰胆碱酯酶活性。结果表明它们在2.05×10^-5mol／L时有一定的活性，但活性较弱。测定了它们对人胃癌细胞（BGC-823）、人肝癌细胞（KB-7402）和人肝癌细胞（BEL-7402）的抑制活性，结果显示部分化合物具有一定的活性。其IC50为1.62-17.5×10^-5mol／ml。表明在适当的取代苯基和取代胺基配合下，此类化合物可能具有抗癌活性，为进一步的研究工作提供了基础。更多还原

【Abstract】 It’s very important to research new antitumor drugs, It has academic significance and possibility to widely applicate. This paper disclosed the research on the synthesis and biological activities of 2-cyano-3-substitued-phenylacrylic acid derivatives.In this paper a new preparation method for N-substituded cyanoacetamides using cyanoacetic acid and N-substituded amine as materials through DCC coupling was developed. And 10 compounds have been synthesized , with yield 51-90%. The results show that This procedure possesses characters of convenient operation and higher yield and is suitable for preparation of cyanoacetamides of different amine.Using Knoevenagel condensation, 5 2-cyano-3-substituedphenyl acrylic acid （esters） have been prepared using substituded benzaldehydes and cyanoacetic acid（esters）, yield 43.1-95%. And using five substituded benzaldehydes and cyanoaceticamides, 15 compounds including 4 new compounds 2-cyano-3-substituedphenylacrylamide have been synthesized with yield 42-95%. And the synthesized compounds were characterized by IR, ¹H NMR MS and EA. The configuration of the compound（zxm-12） been determined by single crystal diffraction. It is （E） formThe anti-biological activities of acetylcholine enzyme for compounds have all been tested. And it is showed that there are some activities in concentrate of 2.05x10^-5mol/L, but it is not strong. The anti-tumor 1 activities of those compound for human stomach cancer（BGC-823）、liver cancer （KB-7402） and liver cancer （BEL-7402） cell were tested. And as a result, some compounds have weak-middle activities with IC₅₀ 1.62-17.5x10^-5 mol/ml. It is evident from the result this kinds of compounds could have better anti-tumor activities if substituted-phenyl and substituted amide are used proper. It is provided base for further studying.更多还原