{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:39:59Z","timestamp":1782545999083,"version":"3.54.5"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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-(\n            <jats:italic>S<\/jats:italic>\n            )-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (\n            <jats:italic>S<\/jats:italic>\n            )-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 (\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA were 6 to 20 times more active than unmodified (\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA on the basis of their 50% effective concentrations in 2.2.15 cells. The increased antiviral activity appeared to be due in part to the increased uptake and conversion of HDP-(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA to HPMPA diphosphate observed in HepG2 cells in vitro. HDP-(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA retained full activity against HBV mutants resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant resistant to adefovir (N236T) was detected. HDP-(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA is orally bioavailable and provides excellent liver exposure to the drug. Oral treatment of HBV transgenic mice with HDP-(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA, 15M-HDP-(\n            <jats:italic>S<\/jats:italic>\n            )-HPMPA, and ODE-(S)-HPMPA for 14 days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent to that of adefovir dipivoxil.\n          <\/jats:p>","DOI":"10.1128\/aac.00114-09","type":"journal-article","created":{"date-parts":[[2009,4,28]],"date-time":"2009-04-28T01:42:41Z","timestamp":1240882961000},"page":"2865-2870","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Alkoxyalkyl Esters of 9-(\n            <i>S<\/i>\n            )-(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"],"prefix":"10.1128","volume":"53","author":[{"given":"John D.","family":"Morrey","sequence":"first","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent E.","family":"Korba","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology and Immunology, Georgetown University Medical Center, Washington, DC 20007"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Beadle","sequence":"additional","affiliation":[{"name":"San Diego Veterans Medical Research Foundation"},{"name":"Department of Medicine, Division of Infectious Disease, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Wyles","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Y.","family":"Hostetler","sequence":"additional","affiliation":[{"name":"San Diego Veterans Medical Research Foundation"},{"name":"Department of Medicine, Division of Infectious Disease, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.3.678"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.2.332"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm050473m"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(03)00110-4"},{"key":"e_1_3_2_6_2","first-page":"91","volume":"13","year":"1991","unstructured":"De Clercq, E. 1991. 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