8-氮杂嘌呤核苷化合物的合成、表征及生物活性测试

发布时间：2018-03-06 13:23

本文选题：核苷　切入点：8-氮杂嘌呤　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：嘌呤核苷在抗HIV、HBV、肿瘤等方面都扮演着非常重要的角色。例如:地丹诺辛、阿德福韦、恩替卡韦、阿昔洛韦、阿巴卡韦都是已经应用于临床的嘌呤核苷类药物。三氮唑核苷是一种非常好的抗病毒核苷药物,例如利巴韦林是三氮唑核苷里面最具有代表性的核苷药物。利巴韦林是第一个人工合成的具有广谱抗病毒活性的三氮唑核苷类化合物,目前临床上用于抗丙肝病毒治疗。由于三氮唑具有独特的五元杂环结构,在药物、化学、农业等领域应用广泛,而三氮唑核苷的研发也受到药物研究者们广泛关注。8-氮杂嘌呤核苷同时具有嘌呤和三氮唑的特点,在生物系统中显现出较好的抗病毒、抗癌活性,因此引起了药物研究者们广泛关注。本实验室长期致力于新型三氮唑核苷类化合物的研发,旨在寻找具有高效低毒的抗病毒和抗肿瘤活性的核苷类药物小分子。本文设计合成了一系列结构新颖的8-氮杂核苷类化合物,并对每个最终化合物进行了活性测试。一、以2'-β-氟代阿糖为原料,探讨一条通过钯催化脒芳基化-分子内脂酰胺化串联制备8-氮杂次黄嘌呤的方法,并以此合成一系列8-氮杂嘌呤核苷类似物。初步测试了化合物的抗HIV活性和HCV活性。二、以2'-氟-2'-甲基-D-阿拉伯呋喃糖为原料,通过一系列有机合成方法合成相应2'-氟-2'-甲基-D-阿拉伯呋喃糖8-氮杂嘌呤核苷类化合物。对8-氮杂嘌呤碱基进行各种修饰得到扩展的一系列8-氮杂嘌呤核苷衍生物。
[Abstract]:Purine nucleoside anti HIV, HBV, tumor and other aspects play a very important role. For example: didanosine, A Duff Vee, entecavir, A Silowe, abacavir are purine nucleosides have been applied in clinical practice. Three ribavirin is a good antiviral nucleoside drugs, such as Leigh Bhave Lin three Triazole Nucleoside nucleoside drugs were most representative. Leigh Bhave Lin is the first synthetic broad-spectrum antiviral activity of three triazole nucleoside compounds, is currently used to anti HCV therapy. The three triazole has five membered heterocyclic structure, unique in the pharmaceutical, chemical, agriculture and other fields are widely used, and research and development of three triazole nucleoside drugs by researchers concern.8- aza purine nucleoside and with purine and three triazole, showing good antiviral anticancer activity in biological systems. Therefore, caused widespread concern. Drug researchers developed in our laboratory has long been committed to the new three triazole nucleosides and nucleoside drugs to find small molecules with high efficiency and low toxicity of antiviral and antitumor activity. This paper designed and synthesized a series of novel aza 8- nucleosides, and each of the final compounds activity test. A 2'- beta fluoro O sugar as raw material, through a discussion of the palladium catalyzed intramolecular arylation of amidine - lipid amidation series preparation of 8- aza hypoxanthine method to synthesize a series of 8- aza purine nucleoside analogues. The preliminary test of compound anti HIV activity and the activity of HCV. Two, 2'- -2'- -D- Arabia fluorine methyl furan sugar as raw material, through a series of organic synthesis of the corresponding 2'- -2'- -D- Arabia furanoses methyl fluoride 8- aza purine nucleoside compounds on 8-. A series of 8- nitrogen heterosinic nucleoside derivatives are expanded by various modifications of the nitrogenine base.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626

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