Synthesis and antiviral activity of 6-chloropurine arabinoside and its 2'-deoxy-2'-fluoro derivative.
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.
Maruyama
T
T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Sato
Y
Y
Oto
Y
Y
Takahashi
Y
Y
Snoeck
R
R
Andrei
G
G
Witvrouw
M
M
De Clercq
E
E
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D012328:RNA Viruses / Q000187:drug effects; D018139:Simplexvirus / Q000187:drug effects
C104186:6-chloro-9-(2-deoxy-2-fluoroarabinofuranosyl)purine; C104185:6-chloropurine arabinoside; D000998:Antiviral Agents; D001087:Arabinonucleosides