{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:43:28Z","timestamp":1790768608712,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"23","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE-1626172"],"award-info":[{"award-number":["CHE-1626172"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic & Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.bmcl.2020.127539","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T04:43:50Z","timestamp":1599626630000},"page":"127539","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and biological evaluation of 5\u2032-C-methyl nucleotide prodrugs for treating HCV infections"],"prefix":"10.1016","volume":"30","author":[{"given":"Madhuri","family":"Dasari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Pelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savita K.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis C.","family":"Liotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2020.127539_b0005","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd4010","article-title":"Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases","volume":"12","author":"Jordheim","year":"2013","journal-title":"Nat Rev Drug Discov"},{"issue":"10","key":"10.1016\/j.bmcl.2020.127539_b0010","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1021\/acs.accounts.6b00274","article-title":"Discovery and development of the anti-human immunodeficiency virus drug, emtricitabine (Emtriva, FTC)","volume":"49","author":"Liotta","year":"2016","journal-title":"Acc Chem Res"},{"key":"10.1016\/j.bmcl.2020.127539_b0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2019.172747","article-title":"Selected nucleos(t)ide-based prescribed drugs and their multi-target activity","volume":"865","author":"Pastuch-Gawo\u0142ek","year":"2019","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"10.1016\/j.bmcl.2020.127539_b0020","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrd703","article-title":"Strategies in the design of antiviral drugs","volume":"1","author":"De Clercq","year":"2002","journal-title":"Nat Rev Drug Discovery"},{"issue":"2","key":"10.1016\/j.bmcl.2020.127539_b0025","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0163-7258(00)00048-6","article-title":"Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases","volume":"87","author":"Van Rompay","year":"2000","journal-title":"Pharmacol Ther"},{"issue":"11","key":"10.1016\/j.bmcl.2020.127539_b0030","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/cmdc.200900289","article-title":"Aryloxy phosphoramidate triesters: a technology for delivering monophosphorylated nucleosides and sugars into cells","volume":"4","author":"Mehellou","year":"2009","journal-title":"ChemMedChem"},{"issue":"6","key":"10.1016\/j.bmcl.2020.127539_b0035","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"},{"issue":"2","key":"10.1016\/j.bmcl.2020.127539_b0040","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.antiviral.2011.08.015","article-title":"Application of kinase bypass strategies to nucleoside antivirals","volume":"92","author":"Ray","year":"2011","journal-title":"Antiviral Res"},{"issue":"45","key":"10.1016\/j.bmcl.2020.127539_b0045","doi-asserted-by":"crossref","first-page":"6984","DOI":"10.2174\/1381612823666171011104158","article-title":"Metabolism of nucleosides and nucleotides prodrugs","volume":"23","author":"De Schutter","year":"2017","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.bmcl.2020.127539_b0050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2040206618758524","article-title":"Addressing the selectivity and toxicity of antiviral nucleosides","volume":"26","author":"Feng","year":"2018","journal-title":"Antiviral Chem Chemother"},{"issue":"1","key":"10.1016\/j.bmcl.2020.127539_b0055","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3851\/IMP1797","article-title":"Nucleotide prodrugs for HCV therapy","volume":"22","author":"Sofia","year":"2011","journal-title":"Antiv Chem Chemother"},{"issue":"23","key":"10.1016\/j.bmcl.2020.127539_b0060","doi-asserted-by":"crossref","first-page":"10400","DOI":"10.1021\/acs.jmedchem.6b00523","article-title":"Nucleoside phosphate and phosphonate prodrug clinical candidates","volume":"59","author":"Thornton","year":"2016","journal-title":"J Med Chem"},{"issue":"6","key":"10.1016\/j.bmcl.2020.127539_b0065","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1128\/AAC.01546-08","article-title":"The octadecyloxyethyl ester of (S)-9-[3-Hydroxy-2-(phosphonomethoxy) propyl]adenine is a potent and selective inhibitor of hepatitis C virus replication in genotype 1A, 1B, and 2A replicons","volume":"53","author":"Wyles","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"10.1016\/j.bmcl.2020.127539_b0070","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1128\/AAC.00530-12","article-title":"Metabolic activation of the anti-hepatitis C virus nucleotide prodrug PSI-352938","volume":"56","author":"Niu","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"10.1016\/j.bmcl.2020.127539_b0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2005.01.003","article-title":"The 5'-nucleotidases as regulators of nucleotide and drug metabolism","volume":"107","author":"Hunsucker","year":"2005","journal-title":"Pharmacol Ther"},{"issue":"9","key":"10.1016\/j.bmcl.2020.127539_b0080","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bbalip.2009.02.007","article-title":"Phosphatidate degradation: Phosphatidate phosphatases (lipins) and lipid phosphate phosphatases","volume":"1791","author":"Brindley","year":"2009","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"issue":"3","key":"10.1016\/j.bmcl.2020.127539_b0085","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0006-2952(03)00290-9","article-title":"Cytosolic and mitochondrial deoxyribonucleotidases: activity with substrate analogs, inhibitors and implications for therapy","volume":"66","author":"Mazzon","year":"2003","journal-title":"Biochem Pharmacol"},{"issue":"3","key":"10.1016\/j.bmcl.2020.127539_b0090","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF02786348","article-title":"The phospholipase-induced degradation of phosphatidylnucleosides","volume":"26","author":"Novozhilova","year":"2000","journal-title":"Russ J Bioorg Chem"},{"issue":"34","key":"10.1016\/j.bmcl.2020.127539_b0095","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.2174\/0929867311320340005","article-title":"The role of soluble 5'-nucleotidases in the conversion of nucleotide analogs: metabolic and therapeutic aspects","volume":"20","author":"Sk","year":"2013","journal-title":"Curr Med Chem"},{"issue":"11","key":"10.1016\/j.bmcl.2020.127539_b0100","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nrd1877","article-title":"Acyclic nucleoside phosphonates: a key class of antiviral drugs","volume":"4","author":"Clercq","year":"2005","journal-title":"Nat Rev Drug Discovery"},{"issue":"6\u20137","key":"10.1016\/j.bmcl.2020.127539_b0105","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/15257770701490126","article-title":"Synthesis and anti-hiv activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: a comparison of phosphonates and corresponding nucleosides","volume":"26","author":"Mackman","year":"2007","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"issue":"23","key":"10.1016\/j.bmcl.2020.127539_b0110","doi-asserted-by":"crossref","first-page":"8309","DOI":"10.1021\/jm101207e","article-title":"Configuration of the 5\u2032-Methyl group modulates the biophysical and biological properties of locked nucleic acid (LNA) oligonucleotides","volume":"53","author":"Seth","year":"2010","journal-title":"J Med Chem"},{"issue":"4","key":"10.1016\/j.bmcl.2020.127539_b0115","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1021\/jo00109a003","article-title":"5'-Methyl-DNA-A new oligonucleotide analog: synthesis and biochemical properties","volume":"60","author":"Saha","year":"1995","journal-title":"J Organ Chem"},{"key":"10.1016\/j.bmcl.2020.127539_b0120","unstructured":"Deshpande M, Wiles JA, Hashimoto A, Phadke A. Preparation of stabilized nucleotides for medical treatment of hepatitis C, RSV, HSV and as antitumor agents. Achillion Pharmaceuticals, Inc., USA . 2016:104pp."},{"key":"10.1016\/j.bmcl.2020.127539_b0125","series-title":"Preparation of Nucleoside and Nucleotide Analog with Protected Phosphates for Treating Diseases Such as Viral Infections, Cancer, and\/or Parasitic Diseases","first-page":"196","author":"Beigelman","year":"2010"},{"issue":"17","key":"10.1016\/j.bmcl.2020.127539_b0130","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1021\/jo034263y","article-title":"Synthesis of the Phosphoramidite Derivative of 2\u2018-Deoxy-2\u2018-C-\u03b2-methylcytidine","volume":"68","author":"Li","year":"2003","journal-title":"J Organ Chem"},{"issue":"18","key":"10.1016\/j.bmcl.2020.127539_b0135","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1016\/j.bmcl.2017.08.029","article-title":"The discovery of IDX21437: design, synthesis and antiviral evaluation of 2\u2032-\u03b1-chloro-2\u2032-\u03b2-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors","volume":"27","author":"Alexandre","year":"2017","journal-title":"Bioorg Med Chem Lett"},{"issue":"12","key":"10.1016\/j.bmcl.2020.127539_b0140","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1016\/j.bmcl.2012.04.065","article-title":"Synthesis and characterization of 2\u2032-C-Me branched C-nucleosides as HCV polymerase inhibitors","volume":"22","author":"Cho","year":"2012","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2020.127539_b0145","unstructured":"Painter G, Bluemling GR, De La Rosa A, Liotta DC, Kuiper D. Preparation of nucleotide and nucleoside therapeutic compns. and uses related thereto as antiviral agents. Emory University, USA . 2017:270pp."},{"issue":"17","key":"10.1016\/j.bmcl.2020.127539_b0150","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1016\/j.bmc.2015.07.003","article-title":"NMR-based conformational analysis of 2',6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs","volume":"23","author":"da Paixao","year":"2015","journal-title":"Bioorg Med Chem"},{"issue":"18","key":"10.1016\/j.bmcl.2020.127539_b0155","doi-asserted-by":"crossref","first-page":"5158","DOI":"10.1039\/C5OB00427F","article-title":"Aspartic acid based nucleoside phosphoramidate prodrugs as potent inhibitors of hepatitis C virus replication","volume":"13","author":"Maiti","year":"2015","journal-title":"Org Biomol Chem"},{"issue":"13","key":"10.1016\/j.bmcl.2020.127539_b0160","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1021\/jm000035+","article-title":"Synthesis and cytokine modulation properties of pyrrolo[2,3-d]-4-pyrimidone nucleosides","volume":"43","author":"Wang","year":"2000","journal-title":"J Med Chem"},{"issue":"7","key":"10.1016\/j.bmcl.2020.127539_b0165","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1021\/jo500089t","article-title":"Preparation of both C5\u2032 epimers of 5\u2032-C-methyladenosine: reagent control trumps substrate control","volume":"79","author":"Bligh","year":"2014","journal-title":"J Organ Chem"},{"key":"10.1016\/j.bmcl.2020.127539_b0170","series-title":"Preparation of Pyrimidine Nucleoside 5'-Phosphoramidates for the Treatment of Hepatitis B Virus","first-page":"124","author":"De la Rosa","year":"2017"},{"issue":"4","key":"10.1016\/j.bmcl.2020.127539_b0175","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/cmdc.201300500","article-title":"The DiPPro approach: synthesis, hydrolysis, and antiviral activity of lipophilic d4t diphosphate prodrugs","volume":"9","author":"Schulz","year":"2014","journal-title":"ChemMedChem"}],"container-title":["Bioorganic & Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X20306508?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X20306508?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:37:05Z","timestamp":1760773025000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X20306508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":35,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["S0960894X20306508"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2020.127539","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and biological evaluation of 5\u2032-C-methyl nucleotide prodrugs for treating HCV infections","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2020.127539","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"127539"}}