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 ED(50) value of 9.8 mg/kg and TD(50) value of 332.2 mg/kg after intraperitoneally injection to mice, which provided compound 6m with a protective index (TD(50)/ED(50)) of 33.9 in the MES test.
State Key Laboratory of Virology, Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Science, Luojiashan Road, Wuhan 430071, China.
Xianran
X
He
Min
M
Zhong
Tao
T
Zhang
Wen
W
Wu
Zhongyuan
Z
Wu
Yuling
Y
Xiao
Xianming
X
Hu
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D006834:Hydrazines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy
D000927:Anticonvulsants; D006834:Hydrazines