Design and synthesis of bioactive adamantane spiro heterocycles

Spiro[aziridine-2,2′-adamantanes] 1 and 2, spiro[azetidine-2,2′-adamantanes] 3 and 5, spiro[azetidine-3,2′-adamantane] 13, spiro[piperidine-4,2′-adamantanes] 25 and 27, and spiro barbituric analog 18 were synthesized and tested for their anti-influenza A virus properties and for trypanocidal activity. The effect of ring size on potency was investigated. Piperidine 25 showed significant anti-influenza A virus activity, being 12-fold more active than amantadine, about 2-fold more active than rimantadine, and 54-fold more potent than ribavirin. It also proved to be the most active of the compounds tested against bloodstream forms of the African trypanosome, Trypanosoma brucei, being 1.5 times more potent than rimantadine and at least 25 times more active than amantadine.

Graphical abstractThe prime target of this study was to examine the anti-influenza A virus and trypanocidal activity of spiro adamantane analogs 1, 2, 3, 5, 13, 25, 27 and 18 and to correlate their potency to the size of the heterocyclic ring.Figure optionsDownload full-size imageDownload as PowerPoint slide