Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor
Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor
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发现一种非两性离子奥司他韦类似物作为有效的甲型流感神经氨酸酶抑制剂
DOI：
10.1016/j.ejmech.2020.112423
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发表时间：
2020
影响因子：
6.7
通讯作者：
Tian Yongshou
中科院分区：
文献类型：
--
作者：
Zhang Huicong;Wang Kuanglei;Zhu Hongxi;Zhao Xiaodi;Zhao Hongqian;Lei Zaiqiang;Chen Binfeng;Yang Fei;Liu Kemin;Zhang Kun;Wang Jian;Tian Yongshou
大多数神经氨酸酶抑制剂是亲脂性差的两性离子，口服生物利用度差。在这里，我们描述了一个合理的旅程，发现一个非两性离子神经氨酸酶的crossor24含有尿素。它对第1组（H5N1和H1N1）和第2组（H3N2）亚型的神经氨酸酶显示出有效的抑制作用，对H274Y突变体的神经氨酸酶显示出比奥司他韦羧酸盐更强的抑制活性。无论是口服还是静脉注射，化合物24在SD大鼠体内的药动学曲线均较羧酸奥司他韦有所改善。
The most of potent neuraminidase inhibitors as zwitterions with poor lipophilicity suffered from the poor oral bioavailability. Herein, we describe a rational journey to discover a non-zwitterionic neuraminidase inhibitor24acontaining urea. It showed potent inhibitions against neuraminidases from group 1(H5N1 and H1N1) and group 2 (H3N2) subtypes and exhibited more strong inhibitory activities against neuraminidases from H274Y mutants than oseltamivir carboxylate. Whether administrated by orally or intravenous injection, the pharmacokinetic profile of compound24ain SD rats were improved compared to oseltamivir carboxylate.