6-Azathymidine-4′-thionucleosides: synthesis and antiviral evaluation

Abstract

The synthesis of dideoxy-6-azathymidine 4′-thionucleoside 1-(2,3-dideoxy-4-thio-β-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4-thio-β-L-erythro-pentofuranosyl)-(6-azathymidine) (3) and their evaluation against a wide panel of antiviral assays are described. The L-thionucleoside (3) was devoid of antiviral activity. The dideoxy-thionucleoside (2) was moderately active against vaccinia virus (VV) and the herpes simplex virus strains HSV-1 (strain KOS) and HSV-2 (strain G) (MIC 12 μM) and retained inhibitory activity vs a thymidine kinase-deficient strain HSV-1/TK^–, suggesting that (2) is not dependent on viral TK-catalysed phosphorylation for antiviral activity and/or may use an alternative metabolic activation pathway.

Keywords::

• 6-Azathymidine-4′-thionucleosides
• L-nucleoside
• dideoxynucleoside
• antiviral
• thymidine kinase deficient (TK-)

Acknowledgements

MJ acknowledges the Malaysian Government for the award of a PhD studentship. We would like to acknowledge the EPSRC Mass Spectrometry Centre, Swansea, UK for mass spectroscopy data.