title: Synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- 3-substituted pyrrolidine-2,5-dione derivatives.
abstract: The synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- succinimides [I-XXII] differently substituted at the position-3 of imide ring have been described. The profile of pharmacological activity of these compounds was examined by a maximal electroshock (MES) and pentylenetetrazole (scPTZ) tests, whereas their neurotoxicity was determined using a rotarod screen. The results obtained revealed that the anticonvulsant activity depended mainly on the kind of substituents at the position-3 of pyrrolidine-2,5-dione ring. The most active were 3,3-dialkyl-pyrrolidine-2,5-diones [IX-XVIII] as well as compounds with 3-methylcyclohexane moiety as a spiro nucleus at position-3 of the imide ring [I-IV]. The 3-cyclohexylsuccinimides [V-VIII] with cyclohexane ring as a flexible fragment were less active, whereas unsubstituated derivatives [XIX-XXII] were devoid of activity in both tests applied. In addition, the anti-seizure protection depended on the position of methyl group at the pyridine moiety. The most potent were compounds with the methyl substituent at the position-4 [II, VI, XVII] or -6 [XI, XIV]. It should be noted, that in the whole series the most active was 1-(4-methyl-2-pyridinyl)-3-cyclohexyl-pyrrolidne-2,5-dione [VI], which showed the anti-scPTZ protection at the dose of 30 mg/kg.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, 9 Medyczna Str. 30-688 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamiński
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D013388:Succinimides