6-Azathymidine-4'-thionucleosides: synthesis and antiviral evaluation.
The synthesis of dideoxy-6-azathymidine 4'-thionucleoside 1-(2,3-dideoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4-thio-beta-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 microM) 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.
Jasamai
Malina
M
Medicinal Chemistry, Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK.
Balzarini
Jan
J
Simons
Claire
C
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D013872:Thionucleosides; C020235:brivudine; D001973:Bromodeoxyuridine; D015774:Ganciclovir; D013936:Thymidine; D000212:Acyclovir