Synthesis And Anticonvulsant Evaluation Of 4-hydroxy-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one Derivatives

As chronic disease,epilepsy is transitory brain dysfunction which results from abnormal discharge of neurons in brains.Currently,main therapeutic method is pharmacotherapeutics,but existing drug is only effective on 60%-70%patients.So it's meaningful to finding the anti-epilepsy compound which is effective and has low toxicity.Benzazepin has extensive biological activity,whereas one branch is oxo-benzazepin.Benzodiazepine type drug has preferable anti anxiety,sedative-hypnotic and antiepileptic activity,and triazole compounds also have extensive biological activity.Based on similarity principle,we chose 1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one as lead compound,then considering the principles of rational drug design,the hydrogen atom on the forth position is substituted by various substituent groups;according to combination principles,1,2,4-1H-triazole is combined to the 1,2-position,the cyclization product is synthesized and characterized by 1H-NMR,13C-NMR,IR and MS,the structure is further identified.By maximal electric shock method(MES)and sc-PTZ,the neurotoxicity of the target compound is evaluated.Generally,the compound with anticonvulsion in animal experiment shows anti-epilepsy activity in clinical trials.The result in pharmacological experiment shows that the compound 4-hydroxy-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one has greatest anti-MES among all compounds with ED50 is 44.0mg/Kg,PI is 6.4.The anticonvulsion is better than the lead compound(ED50=91.3 and PI is 1.3),which provides experimental evidence for further designation of high effective anti-epilepsy compound.