Design, synthesis, and antiviral activity of novel phosphoramidates

Novel phosphoramidates 8a-b possessing structural features similar to nucleoside phosphonates HPMPA, PMEA, PMEG, and oxathiolane nucleoside BCH-189 were synthesized by chemical methods. The designed molecules exhibited significant antiviral activities. We hypothesized that, as a masked membrane-soluble form of the potential bioactive compounds 7a-b, phosphoramidates 8a-b may act as a proteinase substrate. Then, the potential drug 7a-b 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 8a-b were synthesized as racemates to allow access to both enantiomers.