Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

摘要: The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence drugs on active transport and nucleoside kinase-mediated activation. They are also resistant metabolic deactivation by phosphorolytic enzymes. 39 ProTides FUDR with variation in aryl, ester, amino acid regions. Notably, only certain ProTide motifs successful delivering monophosphate into intact cells. find that retain activity mycoplasma infected cells, unlike FUDR. Data suggest these compounds be worthy further progression.