Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of new tacrine-like analogues

• Published in: Bioorganic & medicinal chemistry 2001-03, Vol.9 (3), p.727-732
• Main Authors: Marco, José L, de los Rı́os, Cristóbal, Carreiras, Marı́a C, Baños, Josep E, Badı́a, Albert, Vivas, Nuria M
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; Biological and medical sciences; Butyrylcholinesterase; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - pharmacology; Cholinesterases - metabolism; Humans; Inhibitory Concentration 50; Kinetics; Medical sciences; Naphthyridines - chemical synthesis; Naphthyridines - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Quinolines - chemical synthesis; Quinolines - pharmacology; Structure-Activity Relationship; Tacrine - analogs & derivatives; Tacrine - chemical synthesis; Tacrine - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(00)00284-4

The synthesis and preliminary results for acetylcholinesterase and butyrylcholinesterase inhibition activity of a series of pyrano[2,3- b]quinolines ( 2, 3) and benzonaphthyridines ( 5, 6) derivatives are described. These molecules are tacrine-like analogues which have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4 H-pyrans and 6-amino-5-cyano-pyridines]-3-carboxylates via Friedländer condensation with selected ketones. These compounds showed moderate acetylcholinesterase inhibition activity, the more potent ( 2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase activity of some of these molecules is also discussed. Graphic