Effect of Structural Modification of the Hydantoin Ring on Anticonvulsant Activity

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Abstract
Selectively substituted hydantoins, 4-hydroxy-2-imidazoloidinones, 2-imidazolones, 2-imidazolidinones, vicinal diamines and simple amino acid derivatives were prepared and evaluated in the maximal electroshock seizure (MES), s.c. pentylenetetrazoleseizure threshold (s.c. Met) and rotorod (Tox) tests in mice and rats. ED50 and the medium toxic dose (TD50) for the most active compounds are reported. In general, the most pronounced activity was observed for hydantoins and protected amino acids. Within each sites of compounds, enhanced anticonvulsant activity was often noted for compounds containing an aromatic group 1 carbon removed from a nitrogen atom. Among the most active compounds observed were the amino acid derivative N-acetyl-DL-alanine benzylamide (6d) and the two 2-imidazolones 4-methyl-1-(phenylmethyl)-1,3-dihydro-2H-imidazol-2-one and 1-phenyl-1,3-dihydro-2H-imidazol-2-one. Compound 6d was slightly more potent in the MES test than phenacemide.