Design and Synthesis of 4-flurophthalimides as potential anticonvulsant agents

Document Type : Research article


1 Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

2 Student Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.


Objective(s): Anticonvulsant activity of phthalimide was discovered in 2000 by molecular hybridization of thalidomide and ameltolide. In our previous research we have reported some new 4-substituted derivatives of phthalimide with good activity against the tonic and clonic seizures
Material and Methods: A series of novel 4-flurophthalimides that designed using bioisosteric replacement were synthesized by condensation of 4-flurophthalic anhydride with appropriate arylamines. The purity of these compounds was determined by TLC and the chemical structures were confirmed by IR and 1H-NMR spectroscopy. Anticonvulsant activity of prepared compounds was evaluated using MES and PTZ models.
Results: Some of designed compounds significantly protected against the PTZ-induce seizure that compound 10 with lipophilic and flexible aromatic moiety was more potent than reference drug phenytoin and was the most potent in this series of phthalimide derivatives. In the MES model prepared phthalimide do not showed efficient activity.
Conclusion: The prepared compounds are active in clonic seizure.


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