Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor.

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 inhibitor 24a containing 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.

Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A.

Influenza A neuraminidase plays an indispensable role in the process of replication and transmission of influenza, so the neuraminidase inhibition can prevent the reproduction of the viruses therefore achieve the effect of treatment of influenza. However, drug resistance of neuraminidase inhibitors such as oseltamivir highlights the need to develop novel structural neuraminidase inhibitors. Here we explored a series of oseltamivir derivatives bearing pyridyl group.

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

A series of -sulfonyl oseltamivir analogues were designed, synthesized, and their inhibitory activities against neuraminidase from H5N1 subtype evaluated. The results indicated that the IC value of compound , an oseltamivir analogue via methyl sulfonylation of C5-, was 3.50 μM.

Design, synthesis, and evaluation of carboxyl-modified oseltamivir derivatives with improved lipophilicity as neuraminidase inhibitors.

In this study, a series of carboxyl-modified oseltamivir analogs with improved lipophilicity were designed and synthesized, and their inhibitory activities against neuraminidase from influenza A virus H5N1 subtype were evaluated. The results demonstrated that compound 5m exhibited potent inhibitory activity (IC = 1.30 ± 0.