Synthesis and anticonvulsant activity of ethyl 1-(2-arylhydrazinecarboxamido)-2,2-dimethylcyclopropanecarboxylate derivatives

In the present study on the development of new anticonvulsants, twenty three 1-(2-arylhydrazinecarboxamido)-2,2-dimethylcyclopropanecarboxylate 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 6g, 6m and 6w showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 6m showed the MES-induced seizures with ED50 value of 9.8 mg/kg and TD50 value of 332.2 mg/kg after intraperitoneally injection to mice, which provided compound 6m with a protective index (TD50/ED50) of 33.9 in the MES test. (C) 2012 Elsevier Masson SAS. All rights reserved.