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

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.

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

6-p-Halophenyl-3-pyrid-4-yl-1,2,4]triazolo3,4-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 corresponding 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-1-yl)phenyl]-3-pyrid-4-yl-1,2,4]triazolo3,4-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.