SYNTHESIS OF POTENTIAL INHIBITORS OF HIV REVERSE TRANSCRIPTASE

这个项目的目的是合成一系列(脱氧) 将作为艾滋病毒抑制剂进行测试的核苷衍生物- 逆转录酶。其基本思想是使用核苷碱基或 (脱氧)核苷相关化合物赋予位点特异性 已知的有毒分子集合体。我们认为有两个 将产生其他益处：(A)(脱氧)核苷残留物 应有助于毒物进入细胞和(B) 亲脂性的增加通常被赋予核苷 通过毒物应增加穿透的概率 对于艾滋病毒来说，中枢神经系统是一个理想的特征.有毒物质 我们计划使用的物质具有中等的化学反应能力，应该 表现为HIV逆转录酶的自杀抑制剂 酶错误地将它们用作底物--一个合理的 可能性，因为这种酶的底物要求 似乎没有很高的特异性。我们计划的有毒物质 使用的物质选自已知的 与细胞毒性有关，而与核苷有关 组件的选择在很大程度上是基于它们的可接受性 作为HIV逆转录酶的底物。

The aim of this project is to synthesize a series of (deoxy) nucleoside derivatives that will be tested as inhibitors of HIV- reverse transcriptase. The basic idea is to use nucleoside bases or (deoxy) nucleoside related compounds to confer site specificity on known toxiphoric molecular assemblies. We believe that two other benefits will accrue: (a) the (deoxy) nucleoside residue should facilitate the entry of the toxiphore into the cell and (b) the increase in lipophilicity generally conferred on the nucleoside by the toxiphore should increase the probability of penetration of the CNS a desireable feature in the case of HIV. The toxiphores that we plan to use have moderate chemical reactivity and should behave as suicide inhibitors of HIV-reverse transcriptase if the enzyme mistakenly utilizes them as substrates - a reasonable possibility since the substrate requirements for this enzyme do not appear to be of high specificity. The toxiphores that we plan to use have been selected from groups of substances known to be associated with cytotoxicity whereas the nucleoside-related components have been chosen largely based on their acceptability as substrates to HIV-reverse transcriptase.