Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virusElectronic supplementary information (ESI) available: Biological experiments, general method of chemistry, synthesis of target compounds, intermediate products, and their characterization. Docking conformation of amantadine and compound 18. See DOI: 10.1039/c4md00515e

Amantadine derivatives have been the only drugs marketed as M2 inhibitors of influenza A for decades. The identification of pinanamine as a novel M2 inhibitor suggests that M2 ion channels can accommodate more types of hydrophobic scaffolds. Herein, we further investigated the M2 ion channels and identified camphor derivatives as new types of M2 inhibitors. Compound 18 was found to be more potent than amantadine against wild-type influenza virus. The molecular docking revealed that compound 18 occupies more space in the M2 ion channel than amantadine and thus exhibits enhanced activity. Amantadine derivatives have been the only drugs marketed as M2 inhibitors of influenza A for decades.