Synthesis of novel 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones as anticonvulsant agents.
A series of 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones were synthesized using 2-amino-5-nitrophenol as a starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox.). The MES test showed that 7-(4-fluorobenzylamino)-2H-1,4-benzoxazin-3(4H)-one 4b was the most potent with ED(50) value of 31.7 mg/kg and protective index (PI=TD(50)/ED(50)) value of 7.2. To explain the possible mechanism of anticonvulsant activity, the compound 4b was tested in sc-PTZ test, isoniazid test and strychnine test.
Piao
Zhong-Tai
ZT
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin Province 133002, China.
Guan
Li-Ping
LP
Zhao
Li-Ming
LM
Piao
Hu-Ri
HR
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D013055:Spectrophotometry, Infrared
D000927:Anticonvulsants; D048588:Benzoxazines