Watanabe K A, Reichman U, Hirota K, Lopez C, Fox J J
J Med Chem. 1979 Jan;22(1):21-4. doi: 10.1021/jm00187a005.
A series of 5-substituted 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines 7a-d and their corresponding uracils 9a-d,f were prepared by condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinosyl bromide (5) with appropriately trimethylsilylated pyrimidines followed by saponification of the protected nucleosides 6 or 8. 1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (7e) was obtained by iodination of 7a. Iodination of 8a followed by removal of the protecting acyl-protecting groups afforded the 5-iodo nucleoside 9e. Several of these 2'-fluoro-substituted nucleosides completely obviated replication of herpes simplex virus type 1 (HSV-1) in monolayers of Vero cells at concentrations of 10-100 microgram/mL. The 5-iodocytosine analogue 7e was the most effective, showing 99.5% suppression of viral replication even at concentrations of 0.1 microgram/mL. The cytotoxicity of 7e to L5178Y or P815 cells in culture was minimal. A comparison of the efficacy of 7e against HSV-1 with other known nucleoside antiviral agents indicates that further in vitro and in vivo evaluation of 7e is warranted.
通过将3-O-乙酰基-5-O-苯甲酰基-2-脱氧-2-氟-D-阿拉伯糖基溴（5）与适当的三甲基硅烷基化嘧啶缩合，然后将受保护的核苷6或8进行皂化反应，制备了一系列5-取代的1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶7a-d及其相应的尿嘧啶9a-d,f。1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）-5-碘胞嘧啶（7e）通过7a的碘化反应制得。8a碘化后去除酰基保护基团得到5-碘核苷9e。这些2'-氟取代核苷中的几种在10-100微克/毫升的浓度下能完全抑制单纯疱疹病毒1型（HSV-1）在Vero细胞单层中的复制。5-碘胞嘧啶类似物7e最为有效，即使在0.1微克/毫升的浓度下也能显示出99.5%的病毒复制抑制率。7e对培养中的L5178Y或P815细胞的细胞毒性极小。将7e对抗HSV-1的功效与其他已知核苷抗病毒剂进行比较表明，有必要对7e进行进一步的体外和体内评估。
