【作者】 李清寒；

【导师】 陈淑华；

【作者基本信息】 四川大学 ， 有机化学， 2003， 硕士

【摘要】 抗菌、抗病毒及抗肿瘤药物的研究是当今药物化学中的热点课题。本文致力于N取代嘌呤及哌嗪羧酸、三氮唑核苷衍生物和缩氨基硫脲类化合物的设计合成及生物活性研究，取得了一些具有重要学术意义和应用前景的创新性结果。 设计合成了9位N取代嘌呤羧酸(酯)8个，N取代哌嗪羧酸5个，三氮唑核苷衍生物4个，缩氨基硫脲化合物18个，共计35个化合物，其中32个为新化合物。所有的目标化合物的结构均经IR，~1HNMR，MS和／或元素分析所确证。深入地研究了9位N取代嘌呤羧酸(酯)，N~4取代哌嗪羧酸及5′位修饰的三氮唑核苷目标物的合成方法，优化了反应条件，实现了简便、高效的合成。 特别深入的研究了微波辐射条件下缩氨基硫脲类化合物的合成方法，优化了反应条件，实现了一条简便、有效、快速、合乎绿色化学原则的合成缩氨基硫脲类化合物的新方法—微波法。该法与经典合成方法相比，显著的缩短了反应时间(微波辐射反应时间比经典法反应时间缩短了16～24倍)，目标物的收率也得到了一定程度的提高，而且溶剂的用量仅为经典法的1／4。 为了验证设计思想，我们将部分目标化合物进行了体外生物活性测试，结果表明4个5′位改造的三氮唑核苷类似化合物中，有两个化合物对流感甲型病毒具有不同程度的抑制作用。这些结果，初步证实了本课题的设计思想具有一定的合理性。为今后深入进行5′位改造的三氮唑核苷类似物抗病毒药物研究提供了重要的借鉴。更多还原

【Abstract】 Studies on synthesis of antibacterial drugs, antiviral drugs and antitumor drugs are a hot field in modern medicinal chemistry. In this paper, the efforts were focused on design and synthesis of 9-N-substitued purine carboxylic acid (ester), 4-N-substitued piperazine carboxylic acid, ribavirin derivatives and thisonsemicarbazones, and study on their bioactivities. A series of useful and creative results have been obtained.35 target compounds (eight compounds of 9-N-substitued purine carboxylic acid (ester), five compounds of 4-N-substitued piperazine carboxylic acid, four compounds of ribavirin analogs and eighteen compounds of thiosemicarbazones ) have been synthesized, which 32 compounds haven’t been reported in literatures. Their chemical structures were confirmed by MS, IR, (1)~HNMR or elemental analysis. The synthetic methods and effect factors of the target compounds have been systematically studied. A series of convenient and efficient reactions have been developed.The synthetic methods of thiosemicarbazones have been systemically investigated, and suitable conditions were chosen. A simple eco-friendly route with high yields has been obtained under microwave irradiation. It significantly decreased in reaction time as compared with the classical methods (The reaction time using microwave irradiation shorten 16-24 times than using classical method).Furthermore, yields of these target compounds have been increased to preferable degrees, and the using volume of solvents under microwave irradiation is only quarter of classical method’s.The part target compounds of preliminary investigation on the bioactivity have been carried out to test our designs. The results of bioactivity in vivo of these target compounds showed that two of the four new 5’-substitued ribavirin analogs had anti-influenza A activities in different degrees. These results had confirmed our preliminary assumption. All of these results offer some important reference to 5’-substitued ribavirin analogs antiviral drug systemically investigated in the future.更多还原