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Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
Alkoxyalkyl Esters Of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent And Selective Inhibitors Of Hepatitis B Virus (Hbv) Replication In Vitro And In Hbv Transgenic Mice In Vivo, John D. Morrey, B E. Korba, J R. Beadle, D L. Wyles, K Y. Hostetler
John D. Morrey
Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more …