Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors

NH2-酰基奥司他韦类似物的合成及作为强效神经氨酸酶抑制剂的生物学评价

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作者:Kuanglei Wang, Fei Yang, Lihui Wang, Kemin Liu, Lu Sun, Bin Lin, Yaping Hu, Boyu Wang, Maosheng Cheng, Yongshou Tian

Abstract

Neuraminidase inhibitors can deter nascent viruses from infecting intact cells by preventing their release from host cells. Herein, a neuraminidase inhibitor 11b absent of basic moieties was discovered in the process of searching for inhibitors targeting 150 cavity. It exhibited potent inhibitions against wild-type neuraminidases from group 1 (H5N1 and H1N1) and group 2 (H7N9) subtypes with IC50 values similar to those of oseltamivir carboxylate. Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC50 values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM). The results were not consistent with the recognized SARs that a basic moiety was an indispensable part of a potent inhibitor.

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