磺酰氨基硫脲及磺酰氨基氰胍类化合物的合成及降血糖活性  

Synthesis and hypoglycemic activity of sulfonaminothioureas and sulfonamino-cyanoguanidines

作　　者：陆才洋[1] 张惠斌[1] 黄文龙[1] 黄莺[1] 李运曼[2] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学生理学教研室,南京210009

出　　处：《中国药科大学学报》2008年第1期7-11,共5页Journal of China Pharmaceutical University

基　　金：国家高技术研究发展计划(“八六三”计划)资助项目(No2003AA2Z3530)~~

摘　　要：目的:研究具有磺酰氨基硫脲和磺酰氨基氰胍结构化合物的合成和降血糖活性。方法:在格列本脲的结构基础上,合成3位取代的1-[4-(4-甲基苯甲酰氨基)乙基]苯磺酰氨基硫脲类化合物(Ⅰ1-6)和3位取代的1-[4-(4-甲基苯甲酰氨基)乙基]苯磺酰氨基氰胍类化合物(Ⅱ1-5),并对所合成的化合物进行四氧嘧啶诱导的高血糖小鼠降血糖活性实验。结果:合成的化合物结构经IR、1HNMR、MS和元素分析等确定;降血糖活性实验结果表明,在所有目标化合物中,多数化合物具有不同程度的降血糖活性,其中化合物Ⅰ6和Ⅱ1的降血糖活性较好。结论:结构中的磺酰脲改为磺酰氨基硫脲和磺酰氨基氰胍,部分化合物的降血糖活性保留,而且3位用长的脂肪链取代时显示更好的生物活性。Aim：To synthesize and characterize a series of sulfonaminothioureas and sulfonaminocyanoguanidines, and to evaluate their biological activities. Methods： Based on the analysis of the chemical structure of glibenclamide, a series of 3-substituted sulfonaminothioureas （Ⅰ1-6） and sulfonaminocyanoguanidines （Ⅱ1-5） were designed and synthesized.Their hypoglycemic activities were evaluated using alloxan-induced hyperglycemia mice model. Results： Their structures were characterized by 1R, ^1H NMR, MS and elemental analysis. It was found that most of the synthesized compounds possessed the activities of blood glucose regulation in the anti-diabetic potency evaluation, of which compound Ⅰ6 and Ⅱ1 showed the most potent activity that is similar to glibenclamide. Conclusion： The activity of glucose regulation could be maintained if the structure of sulfonylurea is substituted by sulfonaminothiourea or sulfonaminocyanognanidine. And those compounds linked with long aliphatic chain in the third position are proved to have more potent activities.

关 键 词：磺酰氨基硫脲 磺酰氨基氰胍 合成 降血糖活性 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]