Abstract
Highly stable and water soluble amino acid phosphomonoester amidates of acyclovir (ACV) were synthesized and shown to function predominantly as prodrugs of AC V and not acyclovir monophosphate (AC V-MP) with activities within two fold of the amino acid prodrug of ACV, valaciclovir (VACV). Metabolism studies revealed that incubation of cell-free extracts of Vero cells with the L-leucine phosphomonoester amidate of ACV (3c), resulted in a burst of ACV-MP production followed by the rapid generation of ACV.