Synthesis and acetylcholinesterase inhibitory evaluation of 4-(1,3-Dioxoisoindolin-2-yl)-N-phenylbenzamide derivatives as potential anti-alzheimer agents

Document Type: Research article

Authors

1 department of medicinal chemsitry, faculty of pharmacy, kermanshah university of medical sciences

2 Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Patients with Alzheimer's disease have cognitive deficits, impaired long-term potentiation and learning and memory. A progressive reduction in cholinergic neurons in some areas of the brain such as cortex and hippocampus is related to the deficits in memory and cognitive function in Alzheimer’s disease (AD). In the current project a new series of phthalimide derivatives were synthesized. Phthalic anhydride was reacted with 4-aminobenzoic acid in the presence of triethylamine under reflux condtion. Then, the obtained acidic derivative was utilized for preparation of final compounds via an amidation reaction through a carbodiimde coupling reaction. Anti-acetylcholinesterase activity of synthesized derivatives was assessed by Ellman's test. Compound 4g in this series exhibited the highest inhibitory potency (IC50 = 1.1 ± 0.25 µM) compared to donepezil (IC50 = 0.41 ± 0.12 µM) as reference drug.

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