Synthesis and anticonvulsant activity of a series of N-substituted bicyclo [2.2.1] hept-5-ene-2,3-dicarboximides.

As part of our study, a series of N-phenyl- and N-benzyl-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximides [III-XVI], structurally related to the previously described N-phenyl- or N-pirydyl-3-arylpyrrolidine-2,5-dione [I, II], were synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and metrazole seizure threshold (sc. MET) tests. The most potent in the maximum electroshock seizure (MES) test were compounds with methyl [III] and chloro [XI] substituents at position -2 of the aromatic ring, whereas of all the synthesized compounds, only N-(2-methoxybenzyl)-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximide [XII] was active in the sc. MET. Compounds with substituents at position -3 or -4 of the aromatic ring were found to be less active [V, VI, XIII and XIV], or devoid of activity [VII, IX, XV and XVI]. In contrast, the N-(4-chlorophenyl)-bicyclo [2.2.1] hept-5-ene-2,3-dicarboximide [VIII] at a dose of 100 mg/kg was active in the MES test.