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Design, synthesis and primary biological evaluation of the novel 2-pyridone derivatives as potent non-nucleoside HBV inhibitors.
European Journal of Medicinal Chemistry 2017 August 19
In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have employed bioisosterism and hybrid pharmacophore-based strategy to explore the chemically diverse space of bioactive compounds. Cytotoxicity, anti-HBV antigen secretion activities and anti-HBV DNA replication activity were assayed with cell counting kit-8 (CCK-8), enzyme linked immunosorbent assay (ELISA) and a real-time PCR, respectively. Some of the new compounds were able to inhibit the replication of HBV DNA activity in the low micromolar range. In particular, compound 8u displayed the most potent activity against the replication of HBV DNA with IC50 value of 3.4 μM. The preliminary structure-activity relationship (SAR) of these new compounds was investigated, which may help designing more potent molecules.
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