title: Synthesis and anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 3-phenyl-pyrrolidine-2,5-dione.
abstract: In the present study, on the development of new anticonvulsants, the series of N-[(4-arylpiperazin-1-yl)-alkyl]-3-(2-methylphenyl)- (8a-e, 10a-h) and 3-(2-trifluoromethyl-phenyl)-pyrrolidine-2,5-diones (9a-e, 11a-i) were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens. Their neurotoxicity were determined applying the rotorod test. In this series, the most active were N-[(4-phenylpiperazin-1-yl)-methyl]-3-(2-trifluoromethylphenyl)-pyrrolidine-2,5-dione (9a) with the ED(50)=20.78mg/kg, when given orally to rats and N-[3-{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-propyl]-3-(2-trifluoromethylphenyl)-pyrrolidine-2,5-dione (11i) with the ED(50)=132.13mg/kg after intraperitoneally injection to mice.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kaminski
authors.forename: Dorota
authors.initials: D
authors.lastname: Skrzynska
authors.forename: Joanna
authors.initials: J
authors.lastname: Pichor
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004597:Electroshock / Q000009:adverse effects; D020258:Neurotoxicity Syndromes; D051381:Rats; D013388:Succinimides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D013388:Succinimides