There is a great need for anti-influenza therapeutics,since influenza is always a major worldwide health threat to humankind.Although amantadine reached the market 40 years ago,amantadine derivatives are the only M2 drugs for influenza virus A,even worse their use is limited in the U.S.because of drug resistance.We initially identified multiple novel M2 inhibitors from a focused screening of a small primary amine library that was designed using a scaffold-hopping strategy based on amantadine.Though these compounds are novel M2 inhibitors and are as active as amantadine against wild type virus,they have no any effect against adamantane-insensitive A/M2 mutants.We further modified the hits and made a series of Pinanamine derivatives,fortunately some of the new compounds were capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants.