Synthesis and Anti-Hepatitis B Activities of 3′-Fluoro-2′-Substituted Apionucleosides

Autor:	Martin Holan, Kathryn Tucker, Natalia Dyatkina, Hong Liu, April Kinkade, Guangyi Wang, Zhinan Jin, Marija Prhavc
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	HBV-antivirals apionucleosides DNA-polymerase inhibition Organic chemistry QD241-441
Zdroj:	Molecules, Vol 27, Iss 8, p 2413 (2022)
Druh dokumentu:	article
ISSN:	1420-3049
DOI:	10.3390/molecules27082413
Popis:	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.
Databáze:	Directory of Open Access Journals
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