Design And Synthesis Of The Urea/Thiourea Derivatives Of Norcantharidin And Anticonvulsant Activity

Epilepsy is a syndrome of the disfunction of brain evoked by over-excitement of neurons in local part of the brain. It was characterized by recurrent unprovoked seizures. To find the novel compound which have better convulsant effect and lower toxicity, with a hybrid pharmacophore approach, in this paper we designed and synthesized 3 classes of 31 compounds, which were unreported in previous literatures. The method of the 1 class and 2 class is that norcantharidin condensed with GABA and Glycine, then converted to acyl chloride, then directly reacted with Ammonium Thiocyanate under anhydrous condition. finally condensed with the aniline derivatives; The method of the 3 class is that norcantharidin condensed with the GABA, and converted to acyl chloride, then directly reacted with ammonia to obtain amide, then converted isocyanate, finally condensed with aniline derivatives. The structures of all the products were confirmed by IR, 1H-NMR and HR-MS.The anticonvulsant activity of these compounds were evaluated by subcutaneous pentyleneterazol (scPTZ), subcutaneous picrotoxin (scPIC) and neurotoxicity test (NT), The latency and the death rate were also recorded. The pharmacology test results displayed that most of the compounds have anticonvulsant activities.