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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.

The Design, Synthesis and Antiviral Evaluation of a Series of 5-trimethylsilyl-1-β-d-(arabinofuranosyl) uracil phosphoramidate ProTides