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

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. 1–2 Annu...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2009-02, Vol.17 (4), p.1534-1541
Main Authors: Zoidis, Grigoris, Kolocouris, Nicolas, Naesens, Lieve, Clercq, Erik De
Format: Article
Language:English
Subjects:
1,2-Annulated adamantane piperidines
Adamantane - chemical synthesis
Adamantane - chemistry
Adamantane - pharmacology
Animals
Anti-influenza A virus agent
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Dogs
H3N2
Humans
Influenza A Virus, H3N2 Subtype - drug effects
Magnetic Resonance Spectroscopy
Molecular Structure
NMR
Piperidines - chemical synthesis
Piperidines - chemistry
Piperidines - pharmacology
Rimantadine
Rimantadine - chemical synthesis
Rimantadine - pharmacology
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2009.01.009