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  • Title: Novel 6-Aminoquinazolinone Derivatives as Potential Cross GT1-4 HCV NS5B Inhibitors.
    Author: Nasr T, Aboshanab AM, Mpekoulis G, Drakopoulos A, Vassilaki N, Zoidis G, Abouzid KAM, Zaghary W.
    Journal: Viruses; 2022 Dec 12; 14(12):. PubMed ID: 36560772.
    Abstract:
    Chronic hepatitis C virus (HCV) infections are a worldwide medical problem responsible for diverse types of liver diseases. The NS5B polymerase enzyme has become a very interesting target for the development of anti-HCV drugs owing to its fundamental role in viral replication. Here we report the synthesis of a novel series of 1-substituted phenyl-4(1H)-quinazolinone and 2-methyl-1-substituted phenyl-4(1H)-quinazolinone derivatives and evaluate their activity against HCV in HCV subgenomic replicon assays. The biological data revealed that compound 11a showed the highest activity against HCV GT1b at a micromolar concentration (EC50 = 0.984 µM) followed by compound 11b (EC50 = 1.38 µM). Both compounds 11a and 11b had high selectivity indices (SI = CC50/EC50), 160.71 and 71.75, respectively, which make them very interesting candidates for further development of more potent and selective anti-HCV agents.
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