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Synthesis and Anticonvulsant Activity of Ethyl 2,2‐dimethyl‐1‐(2‐substitutedhydrazinecarboxamido) Cyclopropanecarboxylate Derivatives
Author(s) -
Zhong Min,
Zhang Yongmin,
He Xianran
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12310
Subject(s) - anticonvulsant , ed50 , pharmacology , neurotoxicity , chemistry , seizure threshold , toxicity , epilepsy , medicine , biochemistry , organic chemistry , in vitro , psychiatry
In this study on the development of new anticonvulsants, fourteen ethyl 2,2‐dimethyl‐1‐(2‐substitutedhydrazinecarboxamido) cyclopropanecarboxylate derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock, subcutaneous pentylenetetrazole 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 6f and 6k showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 6k showed the maximal electroshock‐induced seizures with ED 50 value of 9.2 mg/kg and TD 50 value of 387.5 mg/kg after intraperitoneally injection to mice, which provided compound 6k with a protective index ( TD 50 / ED 50 ) of 42.1 in the maximal electroshock test.