1. Synthesis and Anti-Hepatitis B Activities of 3′-Fluoro-2′-Substituted Apionucleosides
- Author
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Martin Holan, Kathryn Tucker, Natalia Dyatkina, Hong Liu, April Kinkade, Guangyi Wang, Zhinan Jin, and Marija Prhavc
- Subjects
Hepatitis B virus ,Chemistry (miscellaneous) ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Pharmaceutical Science ,Nucleosides ,Prodrugs ,Physical and Theoretical Chemistry ,Antiviral Agents ,Analytical Chemistry - Abstract
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 IC50 value of 120 nM. In an HBV cell-based assay, the phosphoramidate prodrug 39 demonstrated potent activity with an EC50 value of 7.8 nM.
- Published
- 2022
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