3'-DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS

这项研究的目标是设计和合成一系列 3‘-脱氧嘧啶和嘌呤核苷类似物及其某些 核苷酸加成，2‘，3’-不饱和，2‘，3’-双脱氧-Ara-C 3-脱氮胞苷的衍生物将被合成并评价为 潜在的抗HIV和抗CMV药物。要采用的方法 包括质谱学方法学的发展，以及其他 光谱技术，以及它们的生物学和 生化效应。 最近，一种先导化合物1-(3-脱氧-B-D-苏戊呋喃糖基)胞嘧啶 (3‘-脱氧-阿糖胞苷)的合成及其抗病毒活性 这个实验室里的活动。我们的初步研究表明，3‘- 脱氧-Ara-C不仅具有强大的抗HCMV活性(ED50=0.31ug/mLvs 对于DHPG，ED50=0.92ug/mL)，但在结构上也与DHPG不同。 基于这些发现，3‘-脱氧-Ara-C的5’-单磷酸和三磷酸 将为生化研究做好准备。对这一问题的理解 3‘-脱氧-Ara-C的作用机理可能导致设计和合成 具有更好治疗指数的新型抗病毒药物。

This investigation has as its goal the design and synthesis of a series of 3'-deoxy pyrimidine and purine nucleoside analogs, and some of their nucleotide addition, the 2', 3'-unsaturated, 2', 3'-dideoxy-ara-C derivatives of 3-deazacytidine will be synthesized and evaluated as potential anti-HIV and anti-CMV agents. The approaches to be employed include the development of methodology mass spectrum, and other spectroscopic techniques, and the determination of their biological and biochemical effects. Recently, a lead compound, 1-(3-deoxy-B-D-threopentofuranosyl) cytosine (3'-deoxy-ara-C), has been synthesized and evaluated for its antiviral activity in this laboratory. Our preliminary studies have shown that 3'- deoxy-ara-C not only has potent anti-HCMV activity (ED50 = 0.31 ug/mL vs ED50 = 0.92 ug/mL for DHPG), but also is structurally different from DHPG. Based on these findings, the 5'-mono- and triphosphates of 3'-deoxy-ara-C will be prepared for biochemical studies. The understanding of the mechanism of action of 3'-deoxy-ara-C may lead to the design and synthesis of new antiviral agents with a better therapeutic index.