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Synthesis and Anticonvulsant Activity of 1‐(2‐(8‐(benzyloxy)quinolin‐2‐yl)‐1‐butyrylcyclopropyl)‐3‐Substituted Urea Derivatives
Author(s) -
He Xianran,
Zhong Min,
Yang Jin,
Wu Zhongyuan,
Xiao Yuling,
Guo Hao,
Hu Xianming
Publication year - 2012
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/j.1747-0285.2012.01352.x
Subject(s) - anticonvulsant , pharmacology , neurotoxicity , seizure threshold , chemistry , urea , ed50 , epilepsy , toxicity , medicine , biochemistry , in vitro , organic chemistry , psychiatry
In the present study on the development of new anticonvulsants, 16 new1‐(2‐(8‐(benzyloxy)quinolin‐2‐yl)‐1‐butyrylcyclopropyl)‐3‐substituted urea derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined by applying the rotorod test. Three compounds 7a , 7e , and 7m showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7e showed the maximal electroshock seizure‐induced seizures with ED 50 value of 14.3 mg/kg and TD 50 value of 434 mg/kg after intraperitoneal injection to mice, which provided compound 7e with a protective index (TD 50 /ED 50 ) of 30.3 in the maximal electroshock seizure test.