[Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of acyclic nucleoside phosphonates].

To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates with more potent anti-HBV activity,adefovir dipivoxil was used as lead compound,according to the results of enhanced oral bioavailability and antiviral activities of nucleoside L-amino acid ester prodrugs.Eleven novel L-amino acid ester prodrugs of acyclic nucleoside phosphonates were designed and synthesized,their anti-HBV activities were evaluated in HepG2 2.2.15 cells.Eight compounds exhibited antiviral activity,and compound 11 showed the most potent anti-HBV activity and highest selective index in vitro(EC_(50) 0.095 2 μmol·L~(-1),SI 69523).Moreover,by analyzing the primary structure and activity relationship of these compounds,it could be suggested that L-amino acid ester strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.