Design and synthesis of bioactive adamantanaminoalcohols and adamantanamines

Adamantanamines 16, 18, 21, 24, 27, 28, 30, 32, 35, 36, 37, 40, 46 and 48 were synthesized and tested for anti-influenza A virus and trypanocidal activity. The stereoelectronic requirements for optimal antiviral and trypanocidal potency were investigated. The effect of introducing a hydroxyl group close to the amino group on this class of compounds was examined for the first time. Aminoalcohol 24 proved to be the most active of the compounds tested against influenza A virus, being 6-fold more active than amantadine, equipotent to rimantadine and 26-fold more potent than ribavirin. Aminoalcohols 36 and 37 were found to have considerable activity against bloodstream forms of the African trypanosome, Trypanosoma brucei, being almost 10 times more potent than rimantadine.

Graphical abstractA series of novel adamantane aminoalcohols and adamantanamines were synthesized and tested for anti-influenza A virus and trypanocidal activity. The stereoelectronic requirements for optimal antiviral and trypanocidal potency were investigated. We examined for the first time the effect on M2 binding exerted by introducing the hydroxyl group close to the amino group.Figure optionsDownload full-size imageDownload as PowerPoint slide