Phosphoroamidate derivatives of N,O-nucleosides as inhibitors of reverse transcriptase

Phosphoroamidate derivatives of adenine and 5-fluorouracil N,O-nucleoside analogues have been synthesized as potential antiviral prodrugs. In particular, dimethoxyphenyl phosphates, linked via nitrogen to L-leucine methyl ester were studied. The synthesized compounds were also subjected to in vitro evaluation for their RT inhibition. Results show that phosphoroamidate derivatives, in comparison with their corresponding N,O-nucleosides, present a promising antiviral activity, though of micro-molar order.