Janssen Research and Development, LLC, South San Francisco, CA 94080, USA.
Molecules. 2022 Apr 8;27(8):2413. doi: 10.3390/molecules27082413.
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.
核苷类似物作为抗乙肝病毒药物具有优异的记录。慢性感染需要长期给药，最终导致耐药性。因此，寻找具有新型骨架的核苷非常重要。在这里，我们报告了新型 2'-羟基-和 2'-羟甲基-阿比核苷、和相应的三磷酸酯和磷酰胺酸酯前药的合成。2'-羟甲基-阿比核苷 5 的三磷酸酯 对 HBV 聚合酶表现出很强的抑制作用，IC 值为 120 nM。在基于 HBV 细胞的测定中，磷酰胺酸酯前药 表现出很强的活性，EC 值为 7.8 nM。
