Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants

• New 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-diones were synthesized.
• Anticonvulsant activity of all new synthesized compounds was determined.
• Compound 8a displayed ED50 values of 14.90 mg/kg and >33.55 PI of in the MES test.
• Compound 7d showed ED50 values of 42.30 mg/kg and >3.54 PI of in the scPTZ test.

A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a–7d, 8a–8d, 9a–9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs.

In present study, synthesis and anticonvulsant activity of new 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives were described.Figure optionsDownload as PowerPoint slide