Design and synthesis of 1,2-annulated adamantane piperidines with anti-influenza virus activity

1–2 Annulated adamantane piperidines 4, 6, 16, 17, 19, 23 and 25 were synthesized and evaluated for anti-influenza A virus activity. The stereoelectronic requirements for optimal antiviral potency were investigated. Piperidine 23 proved to be the most active of the compounds tested against influenza A virus, being 3.5-fold more active than amantadine, equipotent to rimantadine and 15-fold more potent than ribavirin. It is noteworthy that piperidine 23 displayed one of the highest selectivity indexes (SI > 732) among aminoadamantanes or other cage structure amines tested till now.

The prime target of this study was to examine the anti-influenza A virus activity of 1,2-annulated adamantane piperidines 4, 6, 16, 17, 19, 23 and 25 and to correlate their potency to the size of the heterocyclic ring and the distance of the amine nitrogen atom from the adamantane skeleton.Figure optionsDownload as PowerPoint slide