Design, Synthesis And Activity Research Of The Anticonvulsant Derivatives Of Norcantharidin

To find the anticonvulsants with lower toxicity and broad spectrum, with a hybrid pharmacophore approach, in this paper we designed and synthesized 4 classes of 35 compounds, which were not reported in previous literature. The method of 2 classes is that norcantharidin condensed with amino acid, then converted to acyl chloride, finally condensed with the aniline derivatives; the method of the other 2 classes is that norcantharidin condensed with the corresponding amino acid, then condensed with hydrazine hydrate(directly condensed or converted to methyl ester and then substituted by hydrazine hydrate), finally condensed with the substituted aldehyde/ketone, 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 test results indicated that most of the compounds have anticonvulsant activities, the hydrazone compounds of class 2 and class 4 were with less neurotoxicity. The compound 4 g was effective at the dose of 30 mg/kg in scPTZ at 0.5 h and 4 h, more potent than the standard drug valproic acid (VPA), and also effective in scPIC, it is a promising compound, which needs further research.