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...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-04, Vol.27 (8), p.2413
Main Authors: Holan, Martin, Tucker, Kathryn, Dyatkina, Natalia, Liu, Hong, Kinkade, April, Wang, Guangyi, Jin, Zhinan, Prhavc, Marija
Format: Article
Language:English
Subjects:
Alcohol
Antiviral Agents - pharmacology
apionucleosides
DNA polymerase
DNA-polymerase inhibition
Drug resistance
HBV-antivirals
Hepatitis B
Hepatitis B virus
Mutation
Nucleoside analogs
Nucleosides
Nucleosides - pharmacology
Phosphorylation
Prodrugs
Prodrugs - pharmacology
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Summary: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, and , corresponding triphosphates and phosphoramidate prodrugs. Triphosphate of 2'-hydroxymethyl-apionucleoside 5 exhibited potent inhibition of HBV polymerase with an IC value of 120 nM. In an HBV cell-based assay, the phosphoramidate prodrug demonstrated potent activity with an EC value of 7.8 nM.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27082413