title: Cholinesterase inhibition by derivatives of 2-amino-4,6-dimethylpyridine.
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.affiliation: Laboratoire de Pharmacologie, Faculté de Médecine, Limoges, France.
authors.forename: J
authors.initials: J
authors.lastname: Debord
authors.forename: P
authors.initials: P
authors.lastname: N'Diaye
authors.forename: J C
authors.initials: JC
authors.lastname: Bollinger
authors.forename: K
authors.initials: K
authors.lastname: Fikri
authors.forename: B
authors.initials: B
authors.lastname: Penicaut
authors.forename: J M
authors.initials: JM
authors.lastname: Robert
authors.forename: S
authors.initials: S
authors.lastname: Robert-Piessard
authors.forename: G
authors.initials: G
authors.lastname: Le Baut
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003198:Computer Simulation; D004593:Electrophorus; D006736:Horses; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase