Synthesis and acetylcholinesterase (AChE) inhibitory activity of some N-substituted-5-chloro-2(3H)- benzoxazolone derivatives

Abstract

ABSTRACT: Alzheimer’s disease is a progressive neurodegenerative disorder of the central nervous system. Acetylcholinesterase inhibition is one of the proposed mechanisms for treatment of Alzheimer’s disease. Currently, acetylcholinesterase inhibitors such as tacrine, donepezil, rivastigmine and galantamine are applied in different stages of Alzheimer’s disease teratment. In recent years, various heterocyclic systems have been used as a skeleton to discover new acetylcholinesterase inhibitors. On the other hand, it is known that the benzoxazolone heterocyclic structure exhibited a wide range of biological activities. In this study, a series N-substituted-5-chloro-2(3H)-benzoxazolone derivatives were synthesized and evaluated their acetylcholinesterase inhibitory activity. These compounds were synthesized by Mannich reaction of 5-chloro-2(3H)-benzoxazolone with the appropriated amines. The acetylcholinesterase inhibitory activity of the title compounds was determined by colorimetric Ellman’s method. The preliminary screening results indicated that 5-chloro-2-(3H)- benzoxazolone scaffold demonstrated different inhibition range against acetylcholinesterase enzyme depending on the structural differences. KEY WORDS: acetylcholinesterase Inhibitory activity, 2(3H)-benzoxazolone, mannich reaction, Ellman’s method, synthesis.