Epilepsy is one of the most prevalent neurological syndromes in the word. The classical anti-epileptic drugs comprise phenobarbital, phenytoin, carbamazepine and valproic acid. All currently approved antiepileptic drugs have dose-related toxicity and idiosyncratic side effects. The search for new antiepileptic drugs with lower toxicities and fewer side effects continues. Among compounds studied for anticonvulsant activity, there are phthalimide derivatives. The phthalimide pharmacophore was developed by Vamecq et al. [1]. As a continuation of our research on phthalimide derivatives [2] now we report on the synthesis and evaluation of anticonvulsant and toxicological profiles of the new phthalimide derivatives.

A series of alkanyl, alkenyl and alkinyl derivatives of phthalimide was prepared starting from phthalimide. Compounds containing 1-3 double bonds or triple bond were screened for anticonvulsant activity in the maximal elektroshock screen (MES) and the subcutaneous pentylenetetrazole (ScPTZ) test according to Anticonvulsant Drug Discovery Program National Institutes of Health, Bethesda. Among the new derivatives evaluated, alkinyl derivative emerged as the most active compound as indicated by the protection in the MES and ScPTZ sreens. Configuration and length of the alkenyl chain influenced the activity. Cycloprpyl ring was beneficial for the MES seizure screen.

This work was partly supported by Project No BBN 501/P/185/F by Polish State Commitee for Scientific Research.

[1] Vamecq J.; Bac P.; Herrenknecht Ch.; Maurois P.; Delcourt p.; Stables J.P.: J. Med. Chem. 2000, 43, 1311-1319.

[2] Marona H.; Kieć-Kononowicz K.: Pharmazie 1998, 53, 9, 603-606.

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