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Title: The design, synthesis and antiviral evaluation of a series of 5-trimethylsilyl-1-beta-D-(arabinofuranosyl)uracil phosphoramidate ProTides
Authors: Mehellou, Youcef ×
Balzarini, Jan
McGuigan, Christopher #
Issue Date: Mar-2010
Publisher: Blackwell Scientific Publications
Series Title: Antiviral Chemistry & Chemotherapy vol:20 issue:4 pages:153-60
Abstract: BACKGROUND: Nucleoside analogues always require phosphorylation to be active. This appears to be a particular limitation for uridine-based nucleosides. Our ProTide method allows the direct use of masked membrane-soluble preformed nucleoside phosphates, bypassing the need for the initial phosphorylation step. We herein applied it to some novel 5-trimethylsilyl arabinosyl uridines. METHODS: 5-Trimethylsilyl-1-beta-D-(arabinofuranosyl)uracil was prepared in six steps starting from uridine, and five phosphoramidate ProTide derivatives were synthesized. These compounds were investigated for activity against a range of DNA and RNA viruses, including herpes simplex virus type-1 and type-2, vaccinia virus and HIV. RESULTS: Overall, these compounds did not show significant antiviral activity against any of the viruses tested. CONCLUSIONS: The inactivity of the ProTides of this nucleoside could correspond with poor ProTide activation in vitro, poor onward metabolism or low activity of the putative monophosphate metabolite.
ISSN: 0956-3202
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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