Derivatives of 2-amino-4,6-dimethylpyridine, aryl(alkyl)carboxamides, thiocarbamides and amidrazones, already known for their anti-inflammatory properties, were found to be moderately active inhibitors of acetyl and butyrylcholinesterase. Quantitative structure-activity relationships showed that the binding affinity was enhanced by the following structural modifications: (1) increase in molecular volume, (2) decrease in the energy of the lowest unoccupied molecular orbital, (3) insertion of a methylene group between the amide carbonyl and the aromatic ring, (4) replacement of the amide oxygen by sulfur. The affinity remained, however, weaker than that of the specific inhibitor 9-amino-1,2,3,4-tetrahydroacridine (tacrine). The association of anti-inflammatory and cholinesterase inhibiting activities within the same compound may prove useful for the treatment of Alzheimer's disease.
        
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Debord J, N'Diaye P, Bollinger JC, Fikri K, Penicaut B, Robert JM, Robert-Piessard S, Le Baut G (1997) Cholinesterase inhibition by derivatives of 2-amino-4,6- dimethylpyridine J Enzyme Inhib12: 13-26
Debord J, N'Diaye P, Bollinger JC, Fikri K, Penicaut B, Robert JM, Robert-Piessard S, Le Baut G (1997) J Enzyme Inhib12: 13-26