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'-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.