[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 (EC50 0.0952 micromol x 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.
Fu
Xiao-Zhong
XZ
School of Pharmacy, Guiyang Medical College, Guiyang 550004, China. xiaozhong_fu@sina.com
Jiang
Sai-Hong
SH
Yang
Yu-She
YS
Ji
Ru-Yun
RY
D000596:Amino Acids / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology
D000596:Amino Acids; D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D011355:Prodrugs