Synthesis and Anticonvulsant Activity of Some N-Phenylphthalimides

Abstract

The anticonvulsant potential of a series of N-phenylphthalimide derivatives has been screened in subcutaneous pentylenetetrazole seizure (scPTZ) and maximal electroshock seizure (MES) tests. Intraperitoneal 4-amino-N-phenylphthalimides were the most potent agents against MES in mice. Referring to the N-(2, 6-dimethyl-phenyl)phthalimide structure, the order of anticonvulsant activity appears to correspond to the phthalimide ring substitution pattern of 4-amino>4-nitro>4-methyl; H>3-nitro; 3-amino. The 4-amino-N-(2-methylphenyl)-phthalimide displays an anti-MES ED₅₀ of 47.61μmol/kg with a protective index (PI) of 4.2.Oral administration to rats of the compounds found to be active in mice showed that the 4-amino-N-(2, 6-dimethylphenyl)phthalimide is the most potent anti-MES agent in rats, exhibiting an ED₅₀ of 25.2μmol/kg and a PI greater than 75. Regarding the nature of the 2 and 6 substituents of the N-phenyl ring, the anticonvulsant efficiencies may be ordered as follows : 2, 6-dimethyl>2-methyl>2-ethyl>2-ethyl-6-methyl>2, 6-diethyl>unsubstituted phenyl ring.N-Phenylphthalimide derivatives seem to have great potential as candidate anticonvulsant drugs.