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

Autor:	Prhavc, Martin Holan, Kathryn Tucker, Natalia Dyatkina, Hong Liu, April Kinkade, Guangyi Wang, Zhinan Jin, Marija
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	HBV-antivirals apionucleosides DNA-polymerase inhibition
Zdroj:	Molecules; Volume 27; Issue 8; Pages: 2413
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:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=multidiscipl::3bcb15de02509181028e9942cece06e5 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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