Maruyama T, Sato Y, Oto Y, Takahashi Y, Snoeck R, Andrei G, Witvrouw M, De Clercq E
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Chem Pharm Bull (Tokyo). 1996 Dec;44(12):2331-4. doi: 10.1248/cpb.44.2331.
6-Chloropurine arabinoside (3a) was obtained by treatment of the 2'-O-acetylated congener (2) with ammonia in methanol. The 3',5'-di-O-tritylated riboside (6) was allowed to react with diethylaminosulfur trifluoride (DAST) in the presence of pyridine to give the 2'-deoxy-2'-fluoroarabinoside (7), from which 6-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)purine (3b) was obtained. The antiviral effects of 3a and 3b were assayed against several DNA and RNA viruses. Only 3a displayed potent activity against varicella-zoster virus (VZV). This antiviral activity was dependent on phosphorylation by the VZV-induced thymidine kinase (TK). Compound 3a showed moderate activity against other DNA viruses, herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus. They were equally active against TK- and TK+ strains of HSV-1, which suggests that the HSV-1-encoded TK does not play a role in the anti-HSV-1 activity. No activity was noted with any of the compounds against various RNA viruses, including human immunodeficiency virus, at subtoxic concentrations.
6-氯嘌呤阿拉伯糖苷（3a）是通过在甲醇中用氨处理2'-O-乙酰化同系物（2）得到的。使3'，5'-二-O-三苯甲基化核糖苷（6）在吡啶存在下与二乙氨基三氟化硫（DAST）反应，得到2'-脱氧-2'-氟阿拉伯糖苷（7），由此得到6-氯-9-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）嘌呤（3b）。测定了3a和3b对几种DNA和RNA病毒的抗病毒作用。只有3a对水痘带状疱疹病毒（VZV）表现出强效活性。这种抗病毒活性依赖于VZV诱导的胸苷激酶（TK）的磷酸化作用。化合物3a对其他DNA病毒，即1型单纯疱疹病毒（HSV-1）、2型单纯疱疹病毒（HSV-2）和痘苗病毒表现出中等活性。它们对HSV-1的TK-和TK+菌株具有同等活性，这表明HSV-1编码的TK在抗HSV-1活性中不起作用。在亚毒性浓度下，没有观察到任何化合物对包括人类免疫缺陷病毒在内的各种RNA病毒有活性。
