Design, synthesis and structure-activity relationship of novel inhibitors against H5N1 hemagglutinin-mediated membrane fusion

► All of the 26 new compounds based on CL-385319 inhibit H5N1 pseudovirus. ► Compound 1l was the most active inhibitor with an IC50 of 0.22 μM ► Mechanism study showed that compound 1l target the H5-typed hemagglutinin. ► 3-Fluoro-5-(trifluoromethyl)benzamide is important for the inhibitory activity.