Find in Library

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, <b>4</b> and <b>5</b>, corresponding triphosphates and phosphoramidate prodrugs. Triphosphate <b>38</b> 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 <b>39</b> demonstrated potent activity with an EC₅₀ value of 7.8 nM.