Synthesis and anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 3-phenyl-pyrrolidine-2,5-dione.
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.
Obniska
Jolanta
J
Department of Medicinal Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Kaminski
Krzysztof
K
Skrzynska
Dorota
D
Pichor
Joanna
J
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*
D000927:Anticonvulsants; D013388:Succinimides