Synthesis and anticonvulsant properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane, 2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione. Part IV.

To continue our systematic SAR studies a series of N-phenylamino derivatives of 2-azaspiro[4.4]nonane-, 2-azaspiro[4.5]decane-, 6-methyl-2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione were synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and subcutaneous metrazole seizure threshold (sc. Met) tests. Among those molecules the most potent were N-(4-methylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [V], N-(2-trifluoromethylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [VI], N-(3-methylphenyl)-amino-2-azaspiro[4.5]decane-1,3-dione [VIII] and N-(4-methylphenyl)-amino-6-methyl-2-azaspiro[4.5]decane-1,3-dione [XIV], which inhibited the seizures mainly in the sc. Met test. The obtained results revealed that anticonvulsant activity depended on the presence and the position of the methyl or trifluoromethyl groups at the aryl moiety, as well as the size and the manner of attachment of the cycloalkyl system at the position-3 of the pyrrolidine-2,5-dione ring.