title: Synthesis and anticonvulsant properties of new acetamide derivatives of phthalimide, and its saturated cyclohexane and norbornene analogs.
abstract: The synthesis and anticonvulsant properties of new piperazine or morpholine acetamides derived from 2-(1,3-dioxoisoindolin-2-yl)-, 2-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl-) and (3,5-dioxo-4-azatricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)-acetic acid were described. Initial anticonvulsant screening was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The neurotoxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective in the MES screen. The most active was 2-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}isoindoline-1,3-dione (12) that revealed protection in the electrically induced seizures at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration in mice respectively. This molecule given orally in rats at a dose of 30 mg/kg was more potent than reference anticonvulsant--phenytoin.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, 9 Medyczna Street, Kraków 30-688, Poland. kaminskik@cm-uj.krakow.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamiński
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
authors.forename: Beata
authors.initials: B
authors.lastname: Wiklik
authors.forename: Dmytro
authors.initials: D
authors.lastname: Atamanyuk
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001896:Boron Compounds / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D001896:Boron Compounds; D003510:Cyclohexanes; D010797:Phthalimides; C506365:Cyclohexane