Mehellou, Youcef  ORCID: https://orcid.org/0000-0001-5720-8513, Balzarini, Jan and McGuigan, Christopher ORCID: https://orcid.org/0000-0001-8409-710X
2010.
The design, synthesis and antiviral evaluation of a series of 5-trimethylsilyl-1-β-D-(arabinofuranosyl)uracil phosphoramidate ProTides.
Antiviral Chemistry & Chemotherapy
20
(4)
, pp. 153-160.
10.3851/IMP1476
|
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-β-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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Pharmacy Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| ISSN: | 09563202 |
| Last Modified: | 17 Oct 2022 10:08 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/6993 |
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