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  • Title: Synthesis and anticonvulsant activity of N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives.
    Author: He X, Zhong M, Zhang T, Wu W, Wu Z, Yang J, Xiao Y, Pan Y, Qiu G, Hu X.
    Journal: Eur J Med Chem; 2010 Dec; 45(12):5870-7. PubMed ID: 20947222.
    Abstract:
    In the present study on the development of new anticonvulsants, twenty new N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives 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. Three compounds 5d, 5j and 5t showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 5j showed the MES-induced seizures with ED50 value of 9.2 mg/kg and TD50 value of 421.6 mg/kg after intraperitoneally injection to mice, which provided compound 5j with a protective index (TD50/ED50) of 45.8 in the MES test.
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