Aryloxy Pivaloyloxymethyl Prodrugs as Nucleoside Monophosphate Prodrugs

Intracellular phosphorylation of
therapeutic nucleoside analogues
into their active triphosphate metabolites is a prerequisite for their
pharmacological activity. However, the initial phosphorylation of
these unnatural nucleosides into their monophosphate derivatives can
be a rate-limiting step in their activation. To address this, we herein
report the development of the aryloxy pivaloyloxymethyl prodrugs (POMtides)
as a novel and effective nucleoside monophosphate prodrug technology
and its successful application to the anticancer nucleoside analogue
5-fluoro-2′-deoxyuridine (FdUR).