Markham A F, Newton C R, Porter R A, Sim I S
Antiviral Res. 1982 Dec;2(6):319-30. doi: 10.1016/0166-3542(82)90001-8.
In an attempt to improve the antiviral efficacy of 5'-amino-2',5'-dideoxy-5-iodouridine (AIdU) the N-acetyl and N,3'-O-diacetyl derivatives were prepared. N-Acetylation of AIdU increased its ability to inhibit the phosphorylation of thymidine by the deoxypyrimidine kinase of herpes simplex virus type 1 (HSV1) while diacetylation had the converse effect. The affinity of the corresponding compounds containing uracil or thymine for virus deoxypyrimidine kinase was also determined. A range of N-acyl-, N-sulphonyl- and N,3'-O-diacyl- derivatives of AIdU were synthesized; enhanced inhibition of deoxypyrimidine kinase by a number of these compounds was observed. The previous observation that 5'-azido-2',5'-dideoxy-5-iodouridine has antiherpetic activity in vivo led us to investigate its 3'-O-acetyl derivative as well as the corresponding compound containing uracil. None of the derivatives described showed antiviral activity in cell culture against HSV1; acylation failed to enhance the potency of AIdU against HSV1 in vivo.
为了提高5'-氨基-2',5'-二脱氧-5-碘尿苷（AIdU）的抗病毒效力，制备了N-乙酰基和N,3'-O-二乙酰基衍生物。AIdU的N-乙酰化增强了其抑制单纯疱疹病毒1型（HSV1）脱氧嘧啶激酶对胸苷磷酸化的能力，而二乙酰化则产生相反的效果。还测定了相应的含尿嘧啶或胸腺嘧啶的化合物对病毒脱氧嘧啶激酶的亲和力。合成了一系列AIdU的N-酰基、N-磺酰基和N,3'-O-二酰基衍生物；观察到其中一些化合物对脱氧嘧啶激酶的抑制作用增强。先前观察到5'-叠氮基-2',5'-二脱氧-5-碘尿苷在体内具有抗疱疹活性，这促使我们研究其3'-O-乙酰基衍生物以及相应的含尿嘧啶化合物。所描述的衍生物在细胞培养中均未显示出对HSV1的抗病毒活性；酰化未能增强AIdU在体内对HSV1的效力。
