Synthesis and Biological Evaluation of NH 2 -Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors

A series of <i>NH</i>₂-sulfonyl oseltamivir analogues were designed, synthesized, and their inhibitory activities against neuraminidase from H5N1 subtype evaluated. The results indicated that the IC₅₀ value of compound <b>4a</b>, an oseltamivir analogue via methyl sulfonylation of C5-<i>NH</i>₂, was 3.50 &#956;M. Molecular docking simulations suggested that <b>4a</b> retained most of the interactions formed by oseltamivir carboxylate moieties and formed an additional hydrogen bond with the methylsulfonyl group. Meanwhile, <b>4a</b> showed high stability towards human liver microsomes. More importantly, <b>4a</b> without basic moieties is not a zwitterion as reported on the general structure of neuraminidase inhibitors. This research will provide valuable reference for the research of new types of neuraminidase inhibitors.

Abstract licence: CC BY

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