Abstract
In this study, sixteen new 5,5-cyclopropanespirohydantoin derivatives were synthesized and tested for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole screens. Their neurotoxicity was determined by the rotarod test. Two compounds 7f and 7n showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7f showed the MES-induced seizures with ED50 value of 8.5 mg/kg and TD50 value of 381.7 mg/kg after intraperitoneally injection to mice, which provided compound 7f with a protective index (TD50/ED50) of 44.9 in the MES test.
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Acknowledgments
This investigation was supported by National Science Foundation of China (NSFC) (Grant No: 21302065), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China and Technology Foundation for Selected Overseas Chinese Scholar, Ministry of Personnel of China.
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Nie, Y., Zhong, M., Gao, Y. et al. Synthesis and potential anticonvulsant activity of new 5,5-cyclopropanespirohydantoin derivatives. Med Chem Res 24, 4207–4216 (2015). https://doi.org/10.1007/s00044-015-1465-y
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DOI: https://doi.org/10.1007/s00044-015-1465-y