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

Abstract 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.