Add time:07/16/2019 Source:sciencedirect.com
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 100 mg/kg in mice and at a dose of 30 mg/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 GABAA receptors were tested in vitro. Moreover, for all compounds obtained the lipophilic properties were determined by use of RP-HPLC method.
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