Synthesis and anticonvulsant activity of 1-(2-(8-(benzyloxy)quinolin-2-yl)-1-butyrylcyclopropyl)-3-substituted urea derivatives.
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.
State Key Laboratory of Virology, Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Science, Wuhan, China. hexianran@yahoo.com.cn
Xianran
X
He
Min
M
Zhong
Jin
J
Yang
Zhongyuan
Z
Wu
Yuling
Y
Xiao
Hao
H
Guo
Xianming
X
Hu
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D003292:Convulsants; D004597:Electroshock; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use*
D000927:Anticonvulsants; D003292:Convulsants; D011804:Quinolines; D014508:Urea; D010433:Pentylenetetrazole