Shealy Y F, O'Dell C A, Arnett G, Shannon W M, Thorpe M C, Riordan J M, Coburn W C
J Med Chem. 1986 Sep;29(9):1720-5. doi: 10.1021/jm00159a026.
Carbocyclic analogues of 5-halocytosine nucleosides were prepared by direct halogenation of the carbocyclic analogues of cytidine, 2'-deoxycytidine, 3'-deoxycytidine, or ara-C. The 5-chloro and 5-bromo derivatives of the cytidine (carbodine) and of the 2'-deoxycytidine analogues and the 5-iodo derivatives of all four of the cytosine nucleoside analogues were prepared. All of the C-5-halocytosine nucleosides, as well as the parent C-cytosine nucleosides, were tested against a strain of herpes simplex virus type 1 (HSV-1) that induces thymidine kinase in host cells. Carbodine, 5-bromocarbodine, C-2'-deoxycytidine, C-5-bromo-2'-deoxycytidine, the four C-5-iodocytosine nucleosides, and C-ara-C inhibited replication of this strain of HSV-1 in cultured cells. Most of these compounds were tested also against the type 2 virus (HSV-2) in vitro and were active. The greatest activity observed was exerted by C-5-iodo-2'-deoxycytidine in inhibiting replication of HSV-1 in L929 cells. In tests against these DNA viruses, carbodine, a ribofuranoside analogue that had been shown previously to be highly active against human influenza A virus in vitro, was the most active compound against HSV-2 and one of the most active compounds against HSV-1 in Vero cells. 5-Bromocarbodine was active against influenza virus, but it was less active than carbodine.
通过对胞苷、2'-脱氧胞苷、3'-脱氧胞苷或阿糖胞苷的碳环类似物进行直接卤化反应，制备了5-卤代胞嘧啶核苷的碳环类似物。制备了胞苷（卡波定）和2'-脱氧胞苷类似物的5-氯和5-溴衍生物，以及所有四种胞嘧啶核苷类似物的5-碘衍生物。对所有C-5-卤代胞嘧啶核苷以及母体C-胞嘧啶核苷，针对一株能在宿主细胞中诱导胸苷激酶的1型单纯疱疹病毒（HSV-1）进行了测试。卡波定、5-溴卡波定、C-2'-脱氧胞苷、C-5-溴-2'-脱氧胞苷、四种C-5-碘胞嘧啶核苷以及C-阿糖胞苷均能抑制该株HSV-1在培养细胞中的复制。这些化合物中的大多数还在体外针对2型病毒（HSV-2）进行了测试，结果显示具有活性。所观察到的最大活性来自C-5-碘-2'-脱氧胞苷对L929细胞中HSV-1复制的抑制作用。在针对这些DNA病毒的测试中，卡波定是一种呋喃核糖苷类似物，此前已证明其在体外对人甲型流感病毒具有高活性，它是在Vero细胞中针对HSV-2活性最高的化合物之一，也是针对HSV-1活性最高的化合物之一。5-溴卡波定对流感病毒有活性，但活性低于卡波定。
