Griengl H, Bodenteich M, Hayden W, Wanek E, Streicher W, Stütz P, Bachmayer H, Ghazzouli I, Rosenwirth B
J Med Chem. 1985 Nov;28(11):1679-84. doi: 10.1021/jm00149a024.
Syntheses of 5-(2-haloethyl)-2'-deoxyuridines, 5-(3-chloropropyl)-2'-deoxyuridines, and 5-(2-chloroethyl)-2'-deoxycytidine are described. The antiviral activities of these compounds were determined in cell culture against herpes simplex virus types 1 and 2. All compounds were shown to possess significant and selective antiviral activity. The most potent derivative, 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), inhibited HSV-1 at concentrations below 0.1 microgram/mL. It exerted measurable inhibitory effects on cell proliferation only at concentrations higher than 100 micrograms/mL. In vivo CEDU reduced the mortality rate of HSV-1-infected mice at concentrations lower than 5 mg/kg per day when given intraperitoneally and orally. Thus, it proved to be more effective in this in vivo model than the reference compounds (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)methyl]guanine (ACV).
本文描述了5-(2-卤代乙基)-2'-脱氧尿苷、5-(3-氯丙基)-2'-脱氧尿苷和5-(2-氯乙基)-2'-脱氧胞苷的合成。在细胞培养中测定了这些化合物对1型和2型单纯疱疹病毒的抗病毒活性。结果表明，所有化合物均具有显著的选择性抗病毒活性。最有效的衍生物5-(2-氯乙基)-2'-脱氧尿苷（CEDU）在浓度低于0.1微克/毫升时就能抑制单纯疱疹病毒1型。只有在浓度高于100微克/毫升时，它才对细胞增殖产生可测量的抑制作用。在体内，当腹腔注射和口服时，CEDU在浓度低于每天5毫克/千克时可降低单纯疱疹病毒1型感染小鼠的死亡率。因此，在这个体内模型中，它被证明比参考化合物（E）-5-(2-溴乙烯基)-2'-脱氧尿苷（BVDU）和9-[(2-羟基乙氧基)甲基]鸟嘌呤（ACV）更有效。
