De Clercq E, Walker R T
Pharmacol Ther. 1984;26(1):1-44. doi: 10.1016/0163-7258(84)90049-4.
5-Vinylpyrimidine nucleosides can be readily synthesized via organometallic intermediates from commercially available nucleosides. Highly potent and selective inhibitors of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) are (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and some related analogs such as (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU) and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC). The selective antiviral action of BVDU is based upon a specific phosphorylation by the virus-encoded deoxythymidine kinase (TK), inhibition of the viral DNA polymerase and/or incorporation into viral DNA. The efficacy of BVDU against HSV-1 and VZV infections has been demonstrated in animal models and phase I clinical trials. Possible limitations in the clinical usefulness of 5-vinylpyrimidine nucleosides in general and BVDU in particular are discussed.
5-乙烯基嘧啶核苷可通过有机金属中间体由市售核苷轻松合成。1型单纯疱疹病毒（HSV-1）和水痘带状疱疹病毒（VZV）的高效选择性抑制剂是（E）-5-（2-溴乙烯基）-2'-脱氧尿苷（BVDU）以及一些相关类似物，如（E）-5-（2-碘乙烯基）-2'-脱氧尿苷（IVDU）、1-β-D-阿拉伯呋喃糖基-（E）-5-（2-溴乙烯基）尿嘧啶（BVaraU）和（E）-5-（2-溴乙烯基）-2'-脱氧胞苷（BVDC）。BVDU的选择性抗病毒作用基于病毒编码的脱氧胸苷激酶（TK）的特异性磷酸化、对病毒DNA聚合酶的抑制和/或掺入病毒DNA。BVDU对HSV-1和VZV感染的疗效已在动物模型和I期临床试验中得到证实。文中讨论了一般情况下5-乙烯基嘧啶核苷尤其是BVDU临床应用中可能存在的局限性。
