水溶性稠杂环均三唑并噻二唑体系的合成及生物活性(I):哌嗪取代衍生物  

Synthesis and Bioactivity of Water-soluble Fused s-Triazolothiadiazole Systems(I):Functionalized Piperazine Derivatives

作　　者：胡国强[1] 侯莉莉[1] 谢松强[1] 杜钢军[1] 黄文龙[2] 张惠斌[2] 

机构地区：[1]河南大学药物研究所,开封475001 [2]中国药科大学新药中心,南京210009

出　　处：《化学学报》2008年第8期980-984,共5页Acta Chimica Sinica

基　　金：国家自然科学基金(No.30070861);河南大学重点科研基金(No.04ZDZR009)资助项目

摘　　要：4-氨基-5-吡啶-4-基-均三唑硫醇(1)在复合催化剂DMAP和TBAB作用下与对卤代苯甲酸经环缩合反应以高收率得到中间体6-(5-氯-3-甲基-1-取代苯基-1H-吡唑-4-基)-3-吡啶-3-基-均三唑并[3,4-b][1,3,4]噻二唑(2a～2c),接着苯环卤原子与取代哌嗪在聚乙二醇催化作用下发生亲核取代反应得到相应的哌嗪游离碱(3a～3c).其中,单取代哌嗪游离碱3a与含功能基的卤代物缩合得到功能基取代的哌嗪衍生物(4a～4g).这些产生的游离碱与盐酸反应得到相应的水溶性盐酸盐.所合成新化合物的结构经元素分析和光谱数据表征,并评价了它们的体外抗菌活性及构效关系.6-p-Halophenyl-3-pyrid-4-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles （2a＇---2c） were synthesized by a composite catalyst of phase transfer catalysts tetrabutylammonium bromide （TBAB） and （4-dimethylaminopyridine （DMAP） via cyclo-condensation of 4-amino-5-pyridin-4-yl-s-triazole-3-thiol （1） with para halogenated benzoic acids in the presence of POCl3 in high yields, and the following nucleophilic substitution of halogen at phenyl ring with substituted piperazine under catalysis of PEG-600 gave the corre- sponding free bases 3a-3c successfully. Among them, mono substituted piperazine free base 3a was reacted with functionalized halides to give corresponding bis-substituted piperazine derivatives 6-[4-（4-substituted piperazin-l-yl）phenyl]-3-pyrid-4-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 4a-4g. These yielded piperazine free bases were treated with hydrochloride to the respective HCl salts. The structures of new compounds synthesized were characterized by elemental analysis and spectral data, and their in vitro antibacterial activity and structure-activity relationships were also evaluated.

关 键 词：均三唑 均三唑并噻=唑 哌嗪 抗菌活性:构效关系 

分 类 号：R914[医药卫生—药物化学]