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The hydrophobic side chain of oseltamivir influences type A subtype selectivity of Neuraminidase inhibitors

tetano

Editor, Senior Moderator
Chem Biol Drug Des. 2017 Jun 24. doi: 10.1111/cbdd.13060. [Epub ahead of print]
[h=1]The hydrophobic side chain of oseltamivir influences type A subtype selectivity of Neuraminidase inhibitors.[/h] Lin X[SUP]1,[/SUP][SUP]2[/SUP], Qin-Hua C[SUP]2[/SUP], Peng L[SUP]2[/SUP], Chun-Lei L[SUP]1,[/SUP][SUP]2[/SUP], Guang-De Y[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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 oseltavimir 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[SUB]50[/SUB] = 0.1 ?0.04μM,H3N2 IC[SUB]50[/SUB] = 0.26?0.18 μM) 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.


[h=4]KEYWORDS:[/h] Anti-Influenza; Neuraminidase Inhibitors; Oseltavimir Derivatives; Selectivity

PMID: 28646621 DOI: 10.1111/cbdd.13060
 
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