Design, Synthesis, and Antiviral Activity of Novel Phosphoramidates

Novel phosphoramidates 8ab possessing structural features similar to nucleoside phosphonates HPMPA, PMEA, PMEG, and oxathiolane nucleoside BCH189 were synthesized by chemical methods. The designed molecules exhibited significant antiviral activities. We hypothesized that, as a masked membranesoluble form of the potential bioactive compounds 7ab, phosphoramidates 8ab may act as a proteinase substrate. Then, the potential drug 7ab will be liberated inside the infected cells.The triphosphate anabolites of each could act as competitive substrates for the HIV reverse transcriptase and terminate DNA synthesis after being incorporated into the growing DNA strand. Phosphoramidates 8ab were synthesized as racemates to allow access to both enantiomers.