Journal of Bioequivalence & Bioavailability

Design, synthesis and anti -HBV activity of L -amino ac id ester prodrugs of acyclic nucleoside phosphonates

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

FU Xiao zhong, JIANG Sai hong, YANG Yu she and JI Ru yun

Scientific Tracks Abstracts: JBB

Abstract:

T o design and synthesis a series of novel L -amino ac id esters prodrugs of acyclic nucleo side phosphonates with more potent anti-HBV activity, adefovir dipivoxil was used a s 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 compounds 11 showed the most potent anti-HBV activity and highest elective index in vitro ( EC 50 0.095 2μmo l.L -1 , S I 69523). Moreover, by analyzing the primary structure and activity relationship of these compounds, it could be suggested that L ?amino acid ester strategy has signifi cant potential in the acyclic nucleoside phosphonates prodrug design