2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase.

摘要: The development of novel inhibitors acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer’s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns their esters phosphorus-based acids were synthesized in yields 72% 92% characterized. They evaluated for vitro inhibition AChE from electric eel BuChE equine serum using modified Ellman’s spectrophotometric method. benzamides exhibited moderate IC50 values narrow concentration range 33.1 85.8 µM. higher (53.5–228.4 µM). majority derivatives inhibit more efficiently than are comparable or superior rivastigmine—an established cholinesterases inhibitor used the treatment Phosphorus-based especially improved activity against 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 This derivative was also most selective BuChE. It caused mixed both acted as pseudo-irreversible inhibitor. Several structure-activity relationships identified, e.g., favouring obtained 5-halogenosalicylic polyhalogenated anilines. Both share convenient physicochemical properties blood-brain-barrier penetration thus central nervous system delivery.