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  • Title: Synthesis and anticonvulsant activity of 1-(8-(benzyloxy)quinolin-2-yl)-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones.
    Author: He X, Zhong M, Zhang T, Yang J, Wu Z, Xiao Y, Guo H, Qiu G, Hu X.
    Journal: Eur J Med Chem; 2012 Feb; 48():338-46. PubMed ID: 22236471.
    Abstract:
    In the present study on the development of new anticonvulsants, 16 new1-(8-(benzyloxy)quinolin-2-yl-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Two compounds 8e and 8j showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 8e showed the MES-induced seizures with ED(50) value of 8.6 mg/kg and TD(50) value of 365.3 mg/kg after intraperitoneally injection to mice, which provided compound 8e with a protective index (TD(50)/ED(50)) of 26.8 in the MES test.
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