Synthesis of novel 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones as anticonvulsant agents.

Zhong-Tai Piao, Li-Ping Guan, Li-Ming Zhao, Hu-Ri Piao, Zhe-Shan Quan

Index: Eur. J. Med. Chem. 43 , 1216-21, (2008)

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Abstract

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.