Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors

A series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially 4-hydroxy-l-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC50 = 1.56–2.71 μM) which are compared to that the NA inhibitor Oseltamivir (IC50 = 1.06 μM), and could be used as lead compoundS in the future.

Structure-based design has led to the synthesis of a series of influenza neuraminidase (NA) inhibitors containing pyrrolidine core. Several compounds exhibit some specific activity against influenza A (H3N2).Figure optionsDownload as PowerPoint slide