Synthesis and evaluation of amino acid ester prodrugs of penciclovir

The synthesis, aqueous solubility and stability, in vitro antiviral activity, and oral bioavailability of the amino acid ester prodrugs of penciclovir, 13-20, 23, and 24, are described. All of the prodrugs were highly soluble (> 100 mg/mL) and sufficiently stable in aqueous solution. The oral bioavailability of O-acetyl-O-L-valylpenciclovir (13) (34%) in mice was comparable to that of famciclovir (33%) and approximately 4-fold higher than that of penciclovir.