{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:06:01Z","timestamp":1784106361230,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>\n                    A series of suitably substituted imidazo[4,5\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]pyridine derivatives was synthesized, starting from 4\u2010amino\u20102\u2010chloropyridine, and their antiviral activity against hepatitis C virus (HCV) genotype 1b (GT1b) was evaluated in Huh5.2 replicon cells. Some of the\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>3<\/jats:sup>\n                    \u2010substituted analogs exhibited potent anti\u2010HCV activity (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.61\u201347.24\u2009\u03bcM), as determined by assessing their individual effects on viral RNA replication and protein expression levels. Among these, the most promising compound\n                    <jats:bold>30b<\/jats:bold>\n                    demonstrated synergistic antiviral activity when combined with clinically approved direct\u2010acting anti\u2010HCV therapies, highlighting its potential utility in combination regimens. These new derivatives were rationally designed to target the nonstructural 4B (NS4B) protein of HCV. Our molecular docking studies reinforced the implication of this mechanism of action, suggesting a binding mode similar to the previously reported and structurally related inhibitors clemizole and anguizole. A conserved hydrophobic pocket within NS4B (encompassing TM1\u20133, the Walker A motif, and the amphipathic helix H1) was identified, supporting the validity of this scaffold for further structure\u2010based optimization. Collectively, our results support further investigation of the imidazo[4,5\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]pyridine scaffold for the rational development of novel anti\u2010HCV agents with potential application in combination therapies aimed at the effective elimination of chronic HCV infection.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70378","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:04:49Z","timestamp":1783969489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Synthesis of Novel Imidazo[4,5\u2010\n                    <i>c<\/i>\n                    ]pyridine Derivatives, Evaluation of Their Activity Against Hepatitis C Virus and In Silico Prediction of Their Binding Mode to NS4B Protein"],"prefix":"10.1002","volume":"21","author":[{"given":"Eftychia","family":"Karampella","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Chemistry Division of Pharmaceutical Chemistry Department of Pharmacy School of Health Sciences National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Mpekoulis","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Division of Pharmaceutical Chemistry Department of Pharmacy School of Health Sciences National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Kolida","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina I.","family":"Kalliampakou","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini P.","family":"Kollia","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4033-5580","authenticated-orcid":false,"given":"Eleni V.","family":"Mikropoulou","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Natural Products Chemistry Department of Pharmacy School of Health Sciences National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Halabalaki","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Natural Products Chemistry Department of Pharmacy School of Health Sciences National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos T.","family":"Chasapis","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry Department of Chemistry National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Vassilaki","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Lougiakis","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Division of Pharmaceutical Chemistry Department of Pharmacy School of Health Sciences National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70216-4"},{"key":"e_1_2_8_3_1","unstructured":"\u201cHepatitis C\u201d. 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