Synthesis of N-thiocarbamoyl derivatives of N-amino nucleic acid bases and their antiviral activity

(1)我们已经合成了一类新的核酸碱基类似物--N-氨基酸碱。在本研究中，这些N-氨基化合物被转化为N-硫代氨基甲酰衍生物，有望成为一类新的抗病毒药物。通式为(芳香族)N-NH-CS-NRR‘，其中R和R’为H、甲基、乙基或丙基。为了开发一类新的烷基化N-亚硝脲，将N-氨基核酸碱基转化为N-氨基甲酰衍生物，再经N-亚硝化反应得到一类新的烷基化N-亚硝基类似物，有望成为一类新型的抗癌药物。这些N-氨基-N-亚硝脲类似物不同于正常的N-烷基-N-亚硝脲，不依赖于pH，导致生物材料发生致命的烷基化反应。这种特性具有治疗肿瘤组织内部的优点，其中pH低于正常器官组织中的pH值。本研究详细介绍了这类N-氨基-N-亚硝脲类似物的合成工艺和化学性质，并对其生物活性包括抗癌活性进行了研究。

(1) We have previously synthesized a new class of nucleic acid base analogs, "N-amino nucleic acid bases". In the present study, these N-amino compounds were converted to N-thiocarbamoyl derivatives, which are expected to be a new class of antiviral agents. A general formula is given as (aromatic) N-NH-CS-NRR', where R and R' are H,methyl, ethyl, or propyl group. The biological activities including antiviral activity are under investigation.(2) In order to develop a new class of alkylating N-nitrosoureas, N-amino nucleic acid bases were converted to N-carbamoyl derivatives, followed by N-nitrosation to afford a new class of alkylating N-nitroso analogs, which are expected to a new class of anticancer agents. These N-aminonitrosourea analogs are distinguished from normal N-alkyl-N-nitrosoureas by pH-independent hydrolysis resulting in lethal alkylations of biomaterials. This property has the advantage of treatment of the inside of tumor tissues where pH is lower that that in the normal organ tissues. The present study provided details on the synthetic procedures and chemical characteristics of this type of N-amino-N-nitrosourea analogs and their biological activities including anticancer activity are under investigation.