Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of acyclic nucleoside phosphonates.
- Author:
Xiao-Zhong FU
1
;
Sai-Hong JIANG
;
Yu-She YANG
;
Ru-Yun JI
Author Information
1. School of Pharmacy, Guiyang Medical College, Guiyang 550004, China. xiaozhong_fu@sina.com
- Publication Type:Journal Article
- MeSH:
Amino Acids;
chemistry;
Antiviral Agents;
chemical synthesis;
pharmacology;
Cell Line, Tumor;
Hepatitis B virus;
drug effects;
Humans;
Liver Neoplasms;
pathology;
virology;
Nucleosides;
chemical synthesis;
pharmacology;
Organophosphonates;
chemical synthesis;
pharmacology;
Prodrugs;
chemical synthesis;
pharmacology
- From:
Acta Pharmaceutica Sinica
2008;43(5):495-503
- CountryChina
- Language:Chinese
-
Abstract:
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.
