Sim I S, Raper R H
Antiviral Res. 1984 Jun;4(3):159-68. doi: 10.1016/0166-3542(84)90015-9.
A number of structurally related 5-substituted pyrimidine 2'-deoxyribonucleosides were tested for antiviral activity against herpes simplex virus types 1 and 2 in cell culture. A minimum inhibitory concentration was determined for each compound and from a comparison of these values a number of conclusions were drawn with regard to those molecular features which enhance or reduce antiviral activity. Analogues in which the 5-substituent was unsaturated and conjugated with the pyrimidine ring were more potent antiviral drugs than the corresponding non-conjugated and alkyl-substituted analogues. The length of the 5-substituent and the nature of any heteroatoms contained within it also affected antiviral activity. When one pair of isomers was examined in more detail, differences in antiviral activity similar to those observed in cell culture occurred in virus-infected mice. The biochemical basis for the greater antiviral activity of the preferred isomer was related to affinity both for virus thymidine kinase and virus DNA polymerase.
对一系列结构相关的5-取代嘧啶2'-脱氧核糖核苷进行了测试，以检测其在细胞培养中对1型和2型单纯疱疹病毒的抗病毒活性。确定了每种化合物的最低抑菌浓度，并通过比较这些值，就那些增强或降低抗病毒活性的分子特征得出了一些结论。5-取代基不饱和且与嘧啶环共轭的类似物比相应的非共轭和烷基取代类似物更具抗病毒活性。5-取代基的长度及其所含任何杂原子的性质也影响抗病毒活性。当更详细地研究一对异构体时，在病毒感染的小鼠中出现了与细胞培养中观察到的类似的抗病毒活性差异。优选异构体具有更高抗病毒活性的生化基础与对病毒胸苷激酶和病毒DNA聚合酶的亲和力有关。
