2. Academic Validation
  3. Design, synthesis and primary biological evaluation of the novel 2-pyridone derivatives as potent non-nucleoside HBV inhibitors

Design, synthesis and primary biological evaluation of the novel 2-pyridone derivatives as potent non-nucleoside HBV inhibitors

  • Eur J Med Chem. 2017 Aug 18:136:144-153. doi: 10.1016/j.ejmech.2017.04.048.
Haiyong Jia 1,  Yang Song 2,  Ji Yu 1,  Peng Zhan 1,  Diwakar Rai 1,  Xiaohong Liang 2,  Chunhong Ma 2,  Xinyong Liu 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China.
  • 2 Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan 250012, Shandong Province, PR China.
  • 3 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address: xinyongl@sdu.edu.cn.
PMID: 28494252 DOI: 10.1016/j.ejmech.2017.04.048
Abstract

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.

Keywords

Bioisosterism; HBV; Heterocycle; Hybrid pharmacophore-based; SAR.

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