Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of acyclic nucleoside phosphonates / 药学学报
Acta Pharmaceutica Sinica
;
(12): 495-503, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-277824
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Antiviral Agents
/
Pathology
/
Pharmacology
/
Virology
/
Prodrugs
/
Chemistry
/
Hepatitis B virus
/
Cell Line, Tumor
/
Organophosphonates
/
Amino Acids
Limits:
Humans
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2008
Type:
Article
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