Synthesis and anticonvulsant activity of 1-(8-(benzyloxy)quinolin-2-yl)-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones

Add time:07/13/2019    Source:sciencedirect.com

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 ED50 value of 8.6 mg/kg and TD50 value of 365.3 mg/kg after intraperitoneally injection to mice, which provided compound 8e with a protective index (TD50/ED50) of 26.8 in the MES test.

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