Symmetrical Diamidates as a Class of Phosphate Prodrugs to Deliver the 5′‐Monophosphate Forms of Anticancer Nucleoside Analogues

We herein report on the application of phosphorodiamidate technology to both pyrimidine and purine nucleosides with anticancer activity. Sixteen symmetrical phosphorodiamidates esterified with natural amino acids such as L‐alanine and glycine were synthesized. All the compounds were evaluated for their cytotoxic activity in a wide panel of solid and leukemic tumour cell lines. In addition, a carboxypeptidase Y assay was performed on a representative phosphorodiamidate in order to reveal the putative bioactivation pathway for the reported phosphorodiamidate‐type prodrugs.