2. Academic Validation
  3. Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors

Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors

  • Eur J Med Chem. 2016 Nov 10:123:202-210. doi: 10.1016/j.ejmech.2016.07.048.
Haiyong Jia 1,  Fuxiang Bai 2,  Na Liu 1,  Xiaohong Liang 2,  Peng Zhan 1,  Chunhong Ma 2,  Xuemei Jiang 3,  Xinyong Liu 4
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 Hepatic Diseases, Jinan Infectious Disease Hospital, Jingshi Road, 173, 250021, Jinan, Shandong, PR China.
  • 4 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: 27484509 DOI: 10.1016/j.ejmech.2016.07.048
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. In this article, the original thiazole platform was replaced with pyrazole scaffold to yield the optimal pharmacophore moieties in order to generate novel non-nucleoside HBV inhibitors with desirable potency. Some of the new compounds were able to inhibit HBV activity in the low micromolar range. In particular, compound 6a3 displayed the most potent activity against the secretion of HBsAg and HBeAg with IC50 of 24.33 μM and 2.22 μM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was investigated, which may help designing more potent molecules.

Keywords

Bioisosterism; HBV; Hybrid pharmacophore-based; Non-nucleoside; SAR.

Figures