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.
Zoidis
Grigoris
G
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Panepistimioupoli-Zografou, Athens, Greece. zoidis@pharm.uoa.gr
Kolocouris
Nicolas
N
Naesens
Lieve
L
De Clercq
Erik
E
D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012299:Rimantadine / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D010880:Piperidines; D012299:Rimantadine; D000218:Adamantane