triphosphates [8, 19, 22]. An analogous mechanism of antiviral action is found for the pyrimidine nucleosides 5-E-(2-bromovinyl)-2'-desoxyuridine [BVDU, (II)] [5, 6] and l-(2'-fluoro-2'-desoxy-~D-arabinofuranosyl)-5-iodocytosine (III) [ii, 22, 24], which exhibit vigorous antiherpetic activity. Acyclic analogs of pyrimidine nucleosides, similar in structure to (Ia) and (Ib), either showed weak activity against
抗病毒作用机制的研究表明 (Ia-c) 的总体趋势是:化合物在感染疱疹病毒的细胞中被病毒
胸苷激酶
磷酸化激活,并在
三磷酸盐存在下抑制病毒
DNA 聚合酶 [8] , 19, 22]。发现
嘧啶核苷 5-E-(2-
溴乙烯基)-
2'-脱氧尿苷 [BVDU, (II)] [5, 6] 和 l-(2'-fluoro-2'-) 具有类似的抗病毒作用机制desoxy-~D-arabinofuranosyl)-5-iodocytosine (III) [ii, 22, 24],表现出强烈的抗疱疹活性。
嘧啶核苷的无环类似物在结构上与 (Ia) 和 (Ib) 相似,要么对 1 型和 2 型单纯疱疹病毒(HSV-1 和 HSV-2)表现出微弱的活性,要么没有活性 [4, 9, 13, 16 -18]。L-(1,3-二羟基丙氧基甲基)
胞嘧啶 (IV) 是最近才合成的;