{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T14:13:48Z","timestamp":1758636828311,"version":"3.41.2"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Influenza viruses belong to the Orthomyxoviridae family and cause acute respiratory distress in humans. The developed drug resistance toward\u00a0existing drugs and the emergence of viral mutants that can escape vaccines mandate the search for novel antiviral drugs. Herein, the synthesis of epimeric 4\u2032\u2010methyl\u20104\u2032\u2010phosphonomethoxy [4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(O\u2010CH<jats:sub>2<\/jats:sub>P\u2550O)] pyrimidine ribonucleosides, their phosphonothioate [4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(O\u2010CH<jats:sub>2<\/jats:sub>P\u2550S)] derivatives, and their evaluation against an RNA viral panel are described. Selective formation of the \u03b1\u2010\n<jats:sc>l<\/jats:sc>\u2010lyxo epimer, [4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b2)\u2010(O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2550O)(OEt)<jats:sub>2<\/jats:sub>)] over the \u03b2\u2010\n<jats:sc>d<\/jats:sc>\u2010ribo epimer [4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b2)\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010(O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2550O)(OEt)<jats:sub>2<\/jats:sub>)] was explained by DFT equilibrium geometry optimizations studies. Pyrimidine nucleosides having the [4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b2)\u2010(O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2550O)(OEt)<jats:sub>2<\/jats:sub>)] framework showed specific activity against influenza A virus. Significant anti\u2010influenza virus A (H1N1 California\/07\/2009 isolate) was observed with the 4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b2)\u2010O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2550O)(OEt)<jats:sub>2<\/jats:sub>\u2010uridine derivative <jats:bold>1<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20094.56\u2009mM, SI<jats:sub>50<\/jats:sub>\u2009&gt;\u200956), 4\u2010ethoxy\u20102\u2010oxo\u20101(2<jats:italic>H<\/jats:italic>)\u2010pyrimidin\u20101\u2010yl derivative <jats:bold>3<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20095.44\u2009mM, SI<jats:sub>50<\/jats:sub>\u2009&gt;\u200943) and the cytidine derivative <jats:bold>2<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20090.81\u2009mM, SI<jats:sub>50<\/jats:sub>\u2009&gt;\u200913), respectively. The corresponding thiophosphonates 4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010Me\u20104\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b2)\u2010(O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2009S)(OEt)<jats:sub>2<\/jats:sub>) and thionopyrimidine nucleosides were devoid of any antiviral activity. This study shows that the 4\u2032\u2010<jats:italic>C<\/jats:italic>\u2010(\u03b1)\u2010Me\u20104\u2032\u2010(\u03b2)\u2010O\u2010CH<jats:sub>2<\/jats:sub>\u2010P(\u2550O)(OEt)<jats:sub>2<\/jats:sub> ribonucleoside can be further optimized to provide potent antiviral agents.<\/jats:p>","DOI":"10.1002\/ardp.202200382","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T05:11:26Z","timestamp":1676524286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design, synthesis, and evaluation of 4\u2032\u2010phosphonomethoxy pyrimidine ribonucleosides as potential anti\u2010influenza agents"],"prefix":"10.1002","volume":"356","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-4988","authenticated-orcid":false,"given":"Abdalla E. A.","family":"Hassan","sequence":"first","affiliation":[{"name":"Applied Nucleic Acids Research Center &amp; Chemistry Department, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend A.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Applied Nucleic Acids Research Center &amp; Chemistry Department, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Islam","family":"Zaki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Port Said University Port Said Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa H.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Port Said University Port Said Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Medhat","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Applied Nucleic Acids Research Center &amp; Chemistry Department, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelfattah Z.","family":"Haikal","sequence":"additional","affiliation":[{"name":"Applied Nucleic Acids Research Center &amp; Chemistry Department, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry and The RNA Institute, University at Albany State University of New York Albany New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reham A. 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