Are the 2-Isomers of the Drug Rimantadine Active Anti-Influenza a Agents?

Abstract

There is a lack of information in the medical chemistry literature concerning the anti-influenza A activity of the drug rimantadine's 2-isomer (2-rimantadine). We now present results showing that, although 2-adamantanamine (2-amantadine) 3 is only moderately active, some 2-rimantadine analogues are effective anti-influenza A virus agents in vitro. The 2-rimantadine analogues and their spirocyclobutane and spirocyclopentane congeners were synthesized through interesting routes. The 2-rimantadine analogues were 2–4 times more potent than rimantadine 2 against influenza virus A H₂N₂ strain; their spirocyclobutane congeners proved equally active to rimanta-dine 2. Two compounds exhibited a similar activity and one of the compounds was was fourfold more potent than rimantadine 2 against H₃N₂ strain.