Synthesis and Anti-Hepatitis B Activities of 3′-Fluoro-2′-Substituted Apionucleosides
Nucleoside analogues have excellent records as anti-HBV drugs. Chronic infections require long-term administration ultimately leading to drug resistance. Therefore, the search for nucleosides with novel scaffolds is of high importance. Here we report the synthesis of novel 2′-hydroxy- and 2′-hydroxy...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025269/ https://www.ncbi.nlm.nih.gov/pubmed/35458620 http://dx.doi.org/10.3390/molecules27082413 |
Sumario: | Nucleoside analogues have excellent records as anti-HBV drugs. Chronic infections require long-term administration ultimately leading to drug resistance. Therefore, the search for nucleosides with novel scaffolds is of high importance. Here we report the synthesis of novel 2′-hydroxy- and 2′-hydroxymethyl-apionucleosides, 4 and 5, corresponding triphosphates and phosphoramidate prodrugs. Triphosphate 38 of 2′-hydroxymethyl-apionucleoside 5 exhibited potent inhibition of HBV polymerase with an IC(50) value of 120 nM. In an HBV cell-based assay, the phosphoramidate prodrug 39 demonstrated potent activity with an EC(50) value of 7.8 nM. |
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