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
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DOI：
10.1016/j.ejmech.2016.07.048
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发表时间：
2016-11-10
影响因子：
6.7
通讯作者：
Liu, Xinyong
中科院分区：
文献类型：
--
作者：
Jia, Haiyong;Bai, Fuxiang;Liu, Xinyong
在我们继续努力寻找具有新结构的有效非核苷类B型肝炎病毒（HBV）抑制剂的过程中，我们采用生物电子等排和基于杂合药效团的策略来探索生物活性化合物的化学多样性空间。在这篇文章中，原来的噻唑平台取代吡唑骨架，以产生最佳的药效团部分，以产生新的非核苷类HBV抑制剂具有理想的效力。一些新化合物能够在低微摩尔范围内抑制HBV活性。特别是化合物6a3显示出最有效的抗HBeAg和HBeAg分泌的活性，IC 50分别为24.33 μ M和2.22 μ M。初步研究了这一系列新化合物的构效关系，为设计更有效的化合物提供理论依据。(C)2016 Elsevier Masson SAS。All rights reserved.
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 HBeAg and HBeAg with IC50 of 24.33 mu M and 2.22 mu M, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was investigated, which may help designing more potent molecules. (C) 2016 Elsevier Masson SAS. All rights reserved.