Title: 6-azapyrimidine-2'-deoxy-4'-thionucleosides: antiviral agents against TK+ and TK- HSV and VZV strains
Authors: Maslen, Hannah L ×
Hughes, David
Hursthouse, Mike
De Clercq, Erik
Balzarini, Jan
Simons, Claire #
Issue Date: Oct-2004
Series Title: Journal of Medicinal Chemistry vol:47 issue:22 pages:5482-91
Abstract: The synthesis of a series of novel 1-(2-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray crystallographic data of the thymidine derivative allowed conformational analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded assemblies for the crystal structure were determined using PLATON software to allow further interpretation of the crystal packing and base interactions. The 6-azapyrimidine nucleosides described were evaluated against a range of viral strains. The thymidine analogue showed pronounced activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations suggest that the compounds may not entirely depend on viral TK-catalyzed phosphorylation for antiviral activity and/or use an alternative metabolic activation pathway, and/or display a unique mechanism of antiviral action by the unmetabolized nucleoside analogue.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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