title: Synthesis, physicochemical and anticonvulsant properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones: part V.
abstract: The synthesis, physicochemical and pharmacological properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane-1,3-dione (8-10), 2-azaspiro[4.5]decane-1,3-dione (11-18) and 3-cyclohexyl-pyrrolidine-2,5-dione (19, 20) derivatives were described. The anticonvulsant properties of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (scPTZ) tests, and their neurotoxicity was determined using a rota-rod test. The most active was N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (9), which exhibited anti-seizure properties in the MES model at a dose of 100mg/kg in mice and at a dose of 30mg/kg in rats. To explain the possible mechanism of action, for chosen active derivatives N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (9), N-[(4-bromophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (10), N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.5]decane-1,3-dione (12) and N-[(4-bromophenyl)-amino]-2-azaspiro[4.5]decane-1,3-dione (13) their influence on GABA(A) receptors were tested in vitro. Moreover, for all compounds obtained the lipophilic properties were determined by use of RP-HPLC method.
authors.affiliation: Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamiński
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dybała
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004597:Electroshock; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D001372:Aza Compounds; D011963:Receptors, GABA-A; D013141:Spiro Compounds; D010433:Pentylenetetrazole