Synthesis and anticonvulsant activity of some N-phenylphthalimides.
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 47.61 mumol/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 25.2 mumol/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.
North France Center for the Study of Childhood Epilepsy, Centre Hospitalier Universitaire, Faculté de Médecine de Lille, France.
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Bailleux
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Vallee
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JP
Nuyts
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Vamecq
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010797:Phthalimides / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D010797:Phthalimides