Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of acyclic nucleoside phosphonates / 药学学报
Xiao-Zhong FU; Sai-Hong JIANG; Yu-She YANG; Ru-Yun JI; Xiao-Zhong FU; Sai-Hong JIANG; Yu-She YANG; Ru-Yun JI.
Acta Pharmaceutica Sinica
; (12): 495-503, 2008.
Artículo
en Zh
| WPRIM | ID: wpr-277824
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.
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WPRO
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