6-Azathymidine-4′-thionucleosides: synthesis and antiviral evaluation
Authors:
Open Access
- 1 January 2008
- journal article
- research article
- Published by Taylor & Francis in Journal of Enzyme Inhibition and Medicinal Chemistry
- Vol. 23 (1) , 56-61
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
This publication has 11 references indexed in Scilit:
- 6-Azapyrimidine-2‘-deoxy-4‘-thionucleosides: Antiviral Agents against TK+ and TK− HSV and VZV StrainsJournal of Medicinal Chemistry, 2004
- Synthesis and biological evaluation of some novel 4′-Thio-l-ribonucleosides with modified nucleobase moietiesBioorganic & Medicinal Chemistry Letters, 2003
- Novel 6-Azapyrimidine-2′-Deoxy-4′-Thionucleosides: Synthesis, Biological Evaluation and Conformational AnalysisAntiviral Chemistry and Chemotherapy, 1999
- Synthesis and Biological Activity of 4′-Thionucleosides of 2-Chloroadenine1Nucleosides and Nucleotides, 1994
- Sulphated Polymers are Potent and Selective Inhibitors of Various Enveloped Viruses, Including Herpes Simplex Virus, Cytomegalovirus, Vesicular Stomatitis Virus, Respiratory Syncytial Virus, and Toga-, Arena- and RetrovirusesAntiviral Chemistry and Chemotherapy, 1990
- Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidinesAntiviral Research, 1987
- A novel selective broad-spectrum anti-DNA virus agentNature, 1986
- Comparative Efficacy of Antiherpes Drugs against Different Strains of Herpes Simplex VirusThe Journal of Infectious Diseases, 1980
- The synthesis of oligoribonucleotides. III. The use of silyl protecting groups in nucleoside and nucleotide chemistry. VIIICanadian Journal of Chemistry, 1979
- A new method for the deoxygenation of secondary alcoholsJournal of the Chemical Society, Perkin Transactions 1, 1975