Example：10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Aryloxy Pivaloyloxymethyl Prodrugs as Nucleoside Monophosphate Prodrugs Journal of Medicinal Chemistry (IF7.446), Pub Date : 2021-11-04, DOI: 10.1021/acs.jmedchem.1c01490 Ashwag S. Alanazi, Ageo Miccoli, Youcef Mehellou
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).