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The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors
Author(s) -
Lin Xiong,
QinHua Chen,
Peng Li,
ChunLei Li,
GuangDe Yang
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13060
Subject(s) - neuraminidase , oseltamivir , selectivity , chemistry , neuraminidase inhibitor , side chain , structure–activity relationship , enzyme , biochemistry , stereochemistry , medicine , in vitro , organic chemistry , covid-19 , polymer , disease , infectious disease (medical specialty) , catalysis
Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C‐5 position amino group of oseltamivir was pointed to 150‐cavity of the neuraminidase in group 1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltamivir scaffold containing lipophilic side chains at the C‐5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC 50 = 0.1 ± 0.04 μ m , H3N2 IC 50 = 0.26 ± 0.18 μ m ) showed better inhibitory activity and selectivity against the group 1 neuraminidase. This study may provide a clue to design of better group 1 neuraminidase inhibitors.