Jones A S, Sayers J R, Walker R T, De Clercq E
Chemistry Department, University of Birmingham, Great Britain.
J Med Chem. 1988 Jan;31(1):268-71. doi: 10.1021/jm00396a043.
Treatment of 3',5'-di-O-acetyl-(E)-5-(2-bromovinyl)-2'-deoxyuridine (2) with p-chlorophenyl phosphorodichloridate and 1,2,4-triazole gave 1-(3,5-di-O-acetyl-2-deoxy-beta-D-erythro-pentofuranosyl)-(E)-5-(2-br o movinyl)- 4-(1,2,4-triazol-1-yl)pyrimidin-2(1H)-one (3). Reaction of 3 with ammonia gave (E)-5-(2-bromovinyl)-2'-deoxycytidine (1), the overall yield from 2 being 60%. A similar 4-(1,2,4-triazol-1-yl) derivative (4) was obtained from 3',5'-di-O-acetyl-thymidine by the use of phosphoryl chloride as the condensing agent. Treatment of thymidine with trimethylsilyl chloride and then with phosphoryl chloride and 1,2,4-triazole gave upon workup 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-methyl-4(1,2,4-triazol -1-yl) pyrimidin-2(1H)-one (5). (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU) when similarly treated gave the corresponding (E)-5-(2-bromovinyl) compound 7. A minor product formed in both cases was a 4-(1,2,4-triazol-1-yl) derivative in which the nucleoside 5'-hydroxyl group had been replaced by chlorine (6 and 8). Whereas compounds 4-6 and 8 did not exhibit a selective antiviral effect, compounds 1-3 and 7 proved almost as active as the reference compound BVDU. In particular, compound 7, the 4-triazolyl derivative of BVDU, would seem worth pursuing for its potential as an inhibitor of herpes simplex virus type 1 and varicella-zoster virus.
用对氯苯基二氯磷酸酯和1,2,4 - 三唑处理3',5'-二 - O - 乙酰基 - (E)-5-(2 - 溴乙烯基)-2'-脱氧尿苷(2)，得到1-(3,5 - 二 - O - 乙酰基 - 2 - 脱氧 - β - D - 赤式 - 戊呋喃糖基)-(E)-5-(2 - 溴乙烯基)-4-(1,2,4 - 三唑 - 1 - 基)嘧啶 - 2(1H)-酮(3)。3与氨反应得到(E)-5-(2 - 溴乙烯基)-2'-脱氧胞苷(1)，从2开始的总产率为60%。通过使用磷酰氯作为缩合剂，从3',5'-二 - O - 乙酰基胸苷得到了类似的4-(1,2,4 - 三唑 - 1 - 基)衍生物(4)。用三甲基氯硅烷处理胸苷，然后用磷酰氯和1,2,4 - 三唑处理，后处理得到1-(2 - 脱氧 - β - D - 赤式 - 戊呋喃糖基)-5 - 甲基 - 4(1,2,4 - 三唑 - 1 - 基)嘧啶 - 2(1H)-酮(5)。(E)-5-(2 - 溴乙烯基)-2'-脱氧尿苷(BVDU)经类似处理得到相应的(E)-5-(2 - 溴乙烯基)化合物7。在这两种情况下形成的次要产物是一种4-(1,2,4 - 三唑 - 1 - 基)衍生物，其中核苷5'-羟基被氯取代(6和8)。虽然化合物4 - 6和8没有表现出选择性抗病毒作用，但化合物1 - 3和7证明几乎与参比化合物BVDU一样具有活性。特别是化合物7，即BVDU的4 - 三唑基衍生物，因其作为单纯疱疹病毒1型和水痘 - 带状疱疹病毒抑制剂的潜力而似乎值得进一步研究。
