新型巯基蛋白酶抑制剂的合成及构效关系

Synthesis and Structure-relationship of a New Kind of Inhibitor of Mercapto-proteinases

对一类新的抗生素 ,即含有四氢 2H 1 ,3,5 噻二嗪 2 硫酮 (tetrahydro 2H 1 ,3,5 thiadiazine 2 thione ,THTT)环的化合物进行研究。根据其基本药效结构 ,该类抗生素的抗菌活性强弱主要取决于C3 位取代基 ,故设计在C3 位进行不同基团取代 ,共设计了 1 4种 3 取代 5 丝氨酸 四氢 2H 1 ,3,5 噻二嗪 2 硫酮化合物 ,经文献检索均未见报道 ,可视为新型化合物。化合物的化学结构经熔点测定、元素分析法、紫外光谱、红外光谱、1H 磁共振加以确定。抗菌活性采用微生物敏感实验进行测定。体外抑菌实验表明 ,大部分化合物对所选常见致病菌有较好的活性及抗菌谱 ,特别是苄基取代的化合物 ,其初步的体外抑菌活性优于阳性对照磺胺嘧啶钠 ,提示对该类化合物值得进一步深入研究。

A new kind of antibiotics containing Tetrahydro-2H-1,3,5-thiadiazine-2-thione(THTT) was studied. According to the basic structure-relationship of THTT, the antimicrobial activity is mainly depended on the C 3-substituents. The structure of these compounds were confirmed by UV, IR, H-NMR and elemental analysis. The in vitro activity of the compounds against 6 kinds of bacteria was tested. The antimicrobial activities of all compounds were more potent than sulfadiazine sodium, especially the benzal-substituent THTT, which suggest that it may be worth studying further.