Synthesis and antiseizure evaluation of isoindoline-1,3-dione derivatives in mice

Medicinal Chemistry Research
2014.0

Abstract

Epilepsy is the most common serious chronic noninfective neurological condition in the world. Despite the presence of various antiepileptic drugs in the market for epileptic patients, the necessity for development and discovery of novel antiepileptic drugs is felt. In fact, only 60–70 % of patients respond to the current drugs, and a high incidence of adverse effects is also observed. In the present study, a new series of phthalimide derivatives (compounds 3a–3m) were synthesized through the reaction of phthalic anhydride and various derivatives of aniline in toluene solvent (Reflux, 24 h). Antiepileptic activity of synthesized compounds (3a–3m) was investigated using two experimental models namely, maximal electroshock (MES) and pentylenetetrazole (PTZ), and the obtained results were compared with diazepam as reference drug. Neurotoxicity of compounds was also evaluated using rotarod model. Compound 3m with para methoxy substituent exhibited the anticonvulsant activity at 15.1 ± 1.53 (12.23–17.96) mg/kg dose in MES model compared to other derivatives. Unfortunately, none of the tested compounds rendered acceptable protection in subcutaneous PTZ model.

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