硫氮杂茚联吡唑的合成及其抗惊厥活性

Synthesis and Anticonvulsant Activities of Benzothiazolyl Dimethylpyrazole Derivatives

根据药物设计原理,设计并合成了一系列二甲吡唑-1,3-硫氮杂茚衍生物(6a^6o),其结构经1 H NMR,13 C NMR,IR和MS(EI)表征。采用动物模型验证了6a^6o的活性。结果表明:当取代基为正丁基、正戊基、邻位氟取代苄基和2,6-二氯取代苄基时,化合物表现出较好的抗癫痫活性。其中化合物6g的活性和保护指数均优于阳性对照药丙戊酸钠,并且在MTT实验中未见明显毒性。

According to the principle of drug design,a series of benzothiazolyl dimethylpyrazole derivatives were designed and synthesized.The structures were characterized by 1 H NMR,13 C NMR,IR and MS(EI).The preliminary biological activities of 6a^6o were investigated by animal model.The results showed that four compounds[substituent groups were n-Bu,n-amyl,o-fluoro substituted benzyl and 2,6-dichloride substituted benzyl,respectively]showed better anticonvulsant activity in maximal electroshock seizure test.Among them,compound 6g showed best activity than the positive control drugs valproate and no obvious toxicity was found in the MTT assay.