Synthesis and anticonvulsant activity of new spirosuccinimides differently substituted at the imide nitrogen atom.

In the present study the series of spirosuccinimides with the aromatic ring at the imide nitrogen atom was synthesized. All the compounds were tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. The neurotoxic properties were determined applying the rotorod test (TOX). The most active were N-(2-methoxyphenyl)- [V] and N-(4-chlorophenyl-amino)-2-azaspiro[4.5]decane-1,3-dione [XI] that inhibited seizures at a dose of 100 mg/kg in the scPTZ and MES tests, respectively. The other derivatives, namely N-(3-methoxyphenyl)- [VI], N-(1-phenylethyl)- [VIII], N-(diphenylmethyl)- [IX], N-(6-aminopyridin-2-yl)- [XII] 2-azaspiro[4.5]decane-1,3-diones, and the compounds with the methyl group at position-3 [XIV, XVII] or at position-4 [XVIII] of the cyclohexane ring showed anti-MES and/or anti-scPTZ protections at doses of 300 mg/kg. The results obtained revealed that anticonvulsant activity depended on the substitution mode of the aromatic ring as well as the kind of spacer between imide nitrogen atom and aromatic system.