Synthesis Of 7-(Benzylamino)-2H-benzo[b][1, 4] Oxazin-3(4H)-Ones With Anticonvulsant Activities

Aim:To find better AEDs,with higher anticonvulsant effect and lower neurotoxicity. Methods:2-amino-5-nitrophenol was cyclization with 2-chloroacetyl chloride to give 7-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one(compound 2).7-amino-2H-benzo[b][1,4]-oxazin-3(4H)-one(compound3) was abtained by the reduction of the compound 2. Compounds 4a-4n were obtained through the condensation reaction of compound 3 with suitable benzaldehyde in benzene and further reduction by sodium borohydride in methanol at room temperature.Compound 5 was synthesized by 7-amino-2H-benzo[b][1,4]oxazin-3(4H)-one(compound 3) and benzoyl chloride.Synthesis of compound 6 and 7 was achieved by reacting compound 4b with dimethyl sulfate.Their anticonvulsant activities were evaluated by the maximal electroshock test(MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test(Tox.).The compound 4b was tested in sc-PZT test,isoniazid test and strychnine test.Result and discussion:We designed and synthesized seventeen new compounds,and the structures of the compounds were confirmed by IR,¹H-NMR and MS spectrum.The MES test showed that 7-(4-fluorobenzylamino)-2H-Benzo[b][1,4]oxazin-3(4H)-one 4b was the most potent with ED₅₀ value of 31.7mg/kg and protective index(PI=TD₅₀/ED₅₀) value of 7.2.