Synthesis and Anticonvulsant Activity of Some N-Phenylphthalimides

概要

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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 ED_<50> 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 ED_<50> 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.
公益社団法人日本薬学会の論文
1994-09-15