Discovery of highly potent agents against influenza A virus.

We previously reported several new M2 inhibitors as active as amantadine against influenza A virus and validated by three types of in vitro assays. Herein, we further modified one of the most potent hits in a viral inhibition assay and conducted structure–activity relationship studies on this scaffold. As a result, compound 8e was identified to be the most potent inhibitor against wild-type influenza A virus, being nearly 240-fold more active than amantadine.