title: Synthesis and anticonvulsant activity of new 1-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]pyrrolidine-2,5-diones.
abstract: Twenty-two new 1-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]pyrrolidine-2,5-diones were synthesized and tested for anticonvulsant activity. Initial anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens in mice. Several compounds were tested additionally in the 6-Hz psychomotor seizure model. The neurotoxicity was determined applying the rotarod test. Excluding one compound, all other molecules were found to be effective in at least one seizure model. The most active were 1-(2-oxo-2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)pyrrolidine-2,5-dione (14), 1-{2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}-3-methylpyrrolidine-2,5-dione (17), 1-{2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}-3,3-dimethylpyrrolidine-2,5-dione (23) and 3,3-dimethyl-1-(2-oxo-2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)pyrrolidine-2,5-dione (26). These compounds showed high activity in the 6-Hz psychomotor seizure test as well as were active in the maximal electroshock and subcutaneous pentylenetetrazole (14 and 23) screens. Initial SAR studies for anticonvulsant activity have been discussed.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. kaminskik@cm-uj.krakow.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamiński
authors.forename: Sabina
authors.initials: S
authors.lastname: Rzepka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D005013:Ethosuximide / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D010672:Phenytoin / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D010879:Piperazines; D013388:Succinimides; D005013:Ethosuximide; D010672:Phenytoin; C031503:phenylpiperazine; D010433:Pentylenetetrazole