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氮杂脱氮嘌呤核苷衍生物合成研究
【作者】 沙耀武；
【导师】 蔡孟深；
【作者基本信息】 北京医科大学 ， 药物化学， 1991， 博士
【摘要】 嘌呤核苷类似物的合成研究一直是一个非常活跃的科研领域。很多嘌呤衍生物核苷都具有较强的生理活性。7-去氮嘌呤核苷已从自然界分离，确定结构及全合成。在多种细胞内的酶系统反应中，7-去氮嘌呤核苷 可取代天然腺苷。经研究证明，在多种生物的代谢过程中，它被摄入核糖核酸(RNA)和脱氧核糖核酸(DNA)中。并对嘌呤碱基的生物合成过程有很强的抑制作用。对多种人体癌细胞的核酸合成过程，也呈现很强抑制作用。对多种病毒的生长也有抑制作用。1-去氮腺嘌呤核苷和3-去氮嘌呤核苷已有合成报导。腺嘌呤核苷的两个氮杂衍生物，2-氮杂腺嘌呤核苷和8-氮杂腺嘌呤核苷都已有合成报导，并都具有抗癌活性。6-硫代次黄嘌呤，作为抗癌药被应用于临床。 目前应用于临床的抗癌药物，由于对癌细胞及正常细胞选择性差，毒副作用大。寻找高活性，低毒副作用的抗癌药物一直是药物合成领域中的一个重要课题。已有很多文献报导1，2，4，-三嗪衍生物有抗肿瘤抗病作用。氮杂脲嘧啶有抗肿瘤活性，各种氮杂去氮嘌呤衍生物有抗肿瘤抗病毒活性。 将嘌呤6-位氨基或氧用6-氮杂代替，必将引起嘌呤环电性效应的改变。我们希望嘌呤环系电荷分布的改变，将能使上述化合物在体内对肿瘤细胞及正常细胞有较好的选择性，以期寻找具有抗肿瘤活性和低毒副作用的新药。 以核酸代谢机理为理论指导，综合考虑已掌握的材料，和就下列三种类型衍物为合成研究对象
【Abstract】 The synthesis of natural nucleoside analogues has been being an active field for pharmaceutical chemists. Many nucleosides of purine derivatives possess high biological activities. 7-Deazapurine nucleoside has been separated from nature, determined and synthesized. It can replace natural purine nucleoside in many enzyme reaction systems of cell, and shows strong inhibitting action on the synthesis of natural purine bases. 1-De-azapurine nucleoside and 3-deazapurine nucleoside have been synthesized. 1-Azapurine nucleoside and 8-azapur-ine nucleoside have also been synthesized and all possess anti-cancer activities. 6-Thiopurine has been used as anti-cancer drug for many years.So far, all anti-cancer drugs used have low sele-ctivities towards cancer cells and normal cells. The searching for drugs which have high biological activities on cancer cells and have low poison effects on normal cells has been being an entising subject in the field of drug synthesis. Many derivatives of 1,2,4-triazine have biological activitives. 3,5-dioxo-2,3,4,5-tetra-hydro-1,2,4-triazine has anti-cancer activity.If the 6-C in the ring is replaced by N, the distribution of electron density of purine ring must be changed. We wish that this change will be able to make such compounds have better selectivity to cancer cells and normal cells, in order to get new drugs which have high anti-cancer activity and low poison effect on normal cells.In the view of metabolism of nucleosides, based on the literature on hand, We designed the following three kinds of nucleosides as aim compounds.