{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:54:25Z","timestamp":1787997265529,"version":"build-2784847793"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1016\/j.bmc.2024.117607","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T11:56:30Z","timestamp":1705751790000},"page":"117607","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Development of tenofovir monobenzyl ester phosphonoamidate prodrugs with improved anti-hepatitis B virus activity and intrahepatic tenofovir enrichment"],"prefix":"10.1016","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9886-802X","authenticated-orcid":false,"given":"Xizheng","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9154-0316","authenticated-orcid":false,"given":"Li","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2024.117607_b0005","first-page":"965","article-title":"Hepatitis B: diagnosis and treatment","volume":"81","author":"Wilkins","year":"2010","journal-title":"Am. Fam. Physician"},{"key":"10.1016\/j.bmc.2024.117607_b0010","first-page":"75","article-title":"Hepatitis B","volume":"69","author":"Lin","year":"2004","journal-title":"Am. Fam. Physician"},{"key":"10.1016\/j.bmc.2024.117607_b0015","unstructured":"World Health Organization. Hepatitis B. Accessed 18 July 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b."},{"key":"10.1016\/j.bmc.2024.117607_b0020","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1053\/j.gastro.2005.11.016","article-title":"Predicting cirrhosis risk based on the level of circulating hepatitis B viral load","volume":"130","author":"Iloeje","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1016\/j.bmc.2024.117607_b0025","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.295.1.65","article-title":"Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level","volume":"295","author":"Chen","year":"2006","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.bmc.2024.117607_b0030","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/hep.22898","article-title":"The natural history of chronic hepatitis B virus infection","volume":"49","author":"McMahon","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.bmc.2024.117607_b0035","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol."},{"key":"10.1016\/j.bmc.2024.117607_b0040","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1128\/AAC.00138-06","article-title":"Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus","volume":"50","author":"Delaney","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bmc.2024.117607_b0045","doi-asserted-by":"crossref","DOI":"10.1177\/2325958220919231","article-title":"A review and clinical understanding of tenofovir: Tenofovir disoproxil fumarate versus tenofovir alafenamide","volume":"19","author":"Wassner","year":"2020","journal-title":"J Int Assoc Provid AIDS Care."},{"key":"10.1016\/j.bmc.2024.117607_b0050","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1021\/acs.jmedchem.7b00734","article-title":"The ProTide Prodrug Technology: From the Concept to the Clinic","volume":"61","author":"Mehellou","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0055","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.xphs.2016.12.003","article-title":"Development of a novel formulation that improves preclinical bioavailability of tenofovir disoproxil fumarate","volume":"106","author":"Watkins","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.bmc.2024.117607_b0060","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.932934","article-title":"Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models","volume":"13","author":"Hong","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bmc.2024.117607_b0065","doi-asserted-by":"crossref","first-page":"10244","DOI":"10.1021\/acs.jmedchem.6b01292","article-title":"Next-generation reduction sensitive lipid conjugates of tenofovir: Antiviral activity and mechanism of release","volume":"59","author":"Giesler","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0070","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1021\/acsmedchemlett.9b00184","article-title":"Design, synthesis, and anti-HBV activity of new bis(l-amino acid) ester tenofovir prodrugs","volume":"10","author":"Wang","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bmc.2024.117607_b0075","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.1128\/AAC.01152-15","article-title":"In vitro virology profile of tenofovir alafenamide, a novel oral prodrug of tenofovir with improved antiviral activity compared to that of tenofovir disoproxil fumarate","volume":"59","author":"Callebaut","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bmc.2024.117607_b0080","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/jac\/dkt532","article-title":"Phase I\/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults","volume":"69","author":"Markowitz","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.bmc.2024.117607_b0085","doi-asserted-by":"crossref","first-page":"34337","DOI":"10.1074\/jbc.M110.161802","article-title":"Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977","volume":"285","author":"Murakami","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0090","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1021\/acs.jmedchem.5b01807","article-title":"Discovery of an orally active and liver-targeted prodrug of 5-fluoro-2'-deoxyuridine for the treatment of hepatocellular carcinoma","volume":"59","author":"Peng","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0095","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1021\/jm9507338","article-title":"Decomposition pathways and in vitro HIV inhibitory effects of isoddA pronucleotides: toward a rational approach for intracellular delivery of nucleoside 5'-monophosphates","volume":"39","author":"Valette","year":"1996","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0100","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1177\/074823378700300407","article-title":"Summary review of the health effects associated with phenol","volume":"3","author":"Bruce","year":"1987","journal-title":"Toxicol. Ind. Health"},{"key":"10.1016\/j.bmc.2024.117607_b0105","first-page":"29","article-title":"Recognizing potential toxicity of phenol","volume":"24","author":"Brancato","year":"1982","journal-title":"Vet. Hum. Toxicol."},{"key":"10.1016\/j.bmc.2024.117607_b0110","unstructured":"Chang, J, Huang, Q, Liu, R, et al. Double-liver-targeting phosphonoamidate and phosphonoamidate prodrugs. U.S. Patent US9156874B2, Oct 13, 2015."},{"key":"10.1016\/j.bmc.2024.117607_b0115","doi-asserted-by":"crossref","first-page":"9493","DOI":"10.1021\/acs.jmedchem.2c00869","article-title":"An O-benzyl phosphonamidate prodrug of tenofovir for the treatment of hepatitis B virus infection","volume":"65","author":"Zhang","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0120","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/cmdc.201600156","article-title":"The ProTides Boom","volume":"11","author":"Mehellou","year":"2016","journal-title":"ChemMedChem"},{"key":"10.1016\/j.bmc.2024.117607_b0125","first-page":"92","article-title":"The pharmacology of benzyl alcohol and its esters","volume":"9","author":"Gruber","year":"1923","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.bmc.2024.117607_b0130","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/0006-2952(66)90178-X","article-title":"Glycine acyltransferase activity in developing rat liver","volume":"15","author":"Brandt","year":"1966","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bmc.2024.117607_b0135","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/10915810152630729","article-title":"Final report on the safety assessment of benzyl alcohol, benzoic acid, and sodium benzoate","volume":"20","author":"Nair","year":"2001","journal-title":"Int. J. Toxicol."},{"key":"10.1016\/j.bmc.2024.117607_b0140","unstructured":"Downs JW, Wills BK. Phenol Toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing; March 13, 2023."},{"key":"10.1016\/j.bmc.2024.117607_b0145","doi-asserted-by":"crossref","first-page":"5S","DOI":"10.1177\/1091581817728996","article-title":"Safety assessment of benzyl alcohol, benzoic acid and its salts, and benzyl benzoate","volume":"36","author":"Johnson","year":"2017","journal-title":"Int. J. Toxicol."},{"key":"10.1016\/j.bmc.2024.117607_b0150","unstructured":"Wang G, Wu H. Tenofovir monobenzyl ester phosphamide prodrug, its preparation method and use thereof. CN Patent CN106188139A, Dec 07, 2016."},{"key":"10.1016\/j.bmc.2024.117607_b0155","unstructured":"Wang G, Wu H. Tenofovir monobenzyl ester phosphamide prodrug, preparation method and use thereof. U.S. Patent US20180127445A1, May 10, 2018."},{"key":"10.1016\/j.bmc.2024.117607_b0160","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1073\/pnas.84.4.1005","article-title":"Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA","volume":"84","author":"Sells","year":"1987","journal-title":"PNAS"},{"key":"10.1016\/j.bmc.2024.117607_b0165","doi-asserted-by":"crossref","first-page":"20387","DOI":"10.1074\/jbc.M116.743138","article-title":"The human ether-a-go-go-related gene (hERG) potassium channel represents an unusual target for protease-mediated damage","volume":"291","author":"Lamothe","year":"2016","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bmc.2024.117607_b0170","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1021\/acs.biochem.9b00530","article-title":"Enzyme-catalyzed kinetic resolution of chiral precursors to antiviral prodrugs","volume":"58","author":"Xiang","year":"2019","journal-title":"Biochemistry"},{"key":"10.1016\/j.bmc.2024.117607_b0175","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1128\/AAC.49.5.1898-1906.2005","article-title":"Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue","volume":"49","author":"Lee","year":"2005","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Bioorganic & Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096808962400021X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S096808962400021X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:25:49Z","timestamp":1760837149000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S096808962400021X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":35,"alternative-id":["S096808962400021X"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2024.117607","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development of tenofovir monobenzyl ester phosphonoamidate prodrugs with improved anti-hepatitis B virus activity and intrahepatic tenofovir enrichment","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2024.117607","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"117607"}}