Identification, Synthesis, and Evaluation of New Neuraminidase Inhibitors

High-throughput screening was performed on similar to 6800 compounds to identify KR-72039 as an inhibitor of H1N1 and H5N1 neuraminidases (NAs). Structureactivity relationship studies led to 3e, which inhibited H5N1 NA with an IC50 of 2.8 mu M and blocked viral replication. Docking analysis shows that compounds bind to loop-430 around the NA active site. Compound 3l additionally inhibited H7N9 NA, making it a dual inhibitor of N1- and N2-type NAs.