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Objective(s): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine (Ach) and therefore, through this mechanism improve the symptoms of AD. Materials and Methods: In the current study, based on the potential inhibitory activity of phthalimide derivatives towards acetylcholinesterase enzyme, a new series of phthalimide-based compounds were synthesized (4a-4e) and anti-acetylcholinesterase effect was assessed using Ellman's test. Compound 4b with 4-Fluorophenyl moiety was the most potent derivative in this series (IC50 = 16.42 ± 1.07 μM). It was shown that, none of the synthesized compounds showed superior inhibitory potency compared to donepezil (0.41 ± 0.09 μM) as a reference drug.   Conclusion: The new synthesized phthalimide based analogs could function as potential acetylcholinesterase inhibitors. Further studies are necessary for development of potent analogs.