| Abstract | 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. |
| Authors | J Debord, P N'Diaye, J C Bollinger, K Fikri, B Penicaut, J M Robert, S Robert-Piessard, G Le Baut
(Affiliation: Laboratoire de Pharmacologie, Faculté de Médecine, Limoges, France.)
|
| Journal | Journal of enzyme inhibition
(J Enzyme Inhib)
Vol. 12
Issue 1
Pg. 13-26
(Apr 1997)
ISSN: 8755-5093 SWITZERLAND |
| PMID | 9204379
(Publication Type: Journal Article)
|
| Chemical References |
- Aminopyridines
- Cholinesterase Inhibitors
- Butyrylcholinesterase
- Acetylcholinesterase
|
| Topics |
- Acetylcholinesterase
(blood, metabolism)
- Aminopyridines
(chemical synthesis, chemistry, metabolism, pharmacology)
- Animals
- Binding Sites
- Butyrylcholinesterase
(blood, metabolism)
- Chemistry, Physical
- Cholinesterase Inhibitors
(chemical synthesis, chemistry, metabolism, pharmacology)
- Computer Simulation
- Electrophorus
- Horses
- Hydrogen-Ion Concentration
- Kinetics
- Software
- Structure-Activity Relationship
|
