1,3,4-噻二唑取代的氮唑类化合物的合成及体外抗真菌活性  

Synthesis and in vitro Antifungal Activity of Azole Compounds Containing 1,3,4-thiadiazole

作　　者：刘丽[1,2] 李新利 柴晓云[2] 赵风兰 孟庆国 LIU Li;LI Xin-li;CHAI Xiao-yun;ZHAO Feng-lan;MENG Qing-guo(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Yantai University,Yantai 264005,China;School of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[1]烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室(烟台大学),山东烟台264005 [2]海军军医大学药学院,上海200433

出　　处：《烟台大学学报（自然科学与工程版）》2021年第1期29-34,共6页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：国家自然科学基金资助项目(21602250);烟台市科技创新发展计划项目(2020XDRH105)。

摘　　要：以取代苯甲醛为原料,硫代氨基脲为亲核试剂,经亲核加成-消除、环合反应,合成2-氨基-5-取代苯基-1,3,4-噻二唑,再与环氧化物中间体1-[2-(2,4-二氟苯基)-2,3-环氧丙基]-1H-1,2,4-三唑反应,得到15个含1,3,4-噻二唑的氮唑类衍生物1-15结构均经1H NMR和MS确证。经文献检索,它们均为新化合物。采用微量液基稀释法评价目标化合物的体外抗真菌活性,结果表明,目标物对除熏烟曲霉菌外的所试菌株均具有较好的体外抑制活性,特别是对白念珠菌。化合物4、9、15抗真菌活性最好,尤其是化合物15,对除熏烟曲霉菌外的所试菌株的MIC80值均小于0.5μg/mL。The synthetic route of the intermediate 2-amino-5-substituted phenyl-1,3,4-thiadiazole is based on the nucleophilic addition-elimination and cyclization reaction from the substituted benzaldehyde and thiosemicarbazide.Then,it undergoes ring-opening reaction with the key intermediate 1-[2-(2,4-difluorophenyl)-2,3-epoxypropyl]-1 H-1,2,4-triazole methanesulfonate.All the fifteen target compounds are all new compounds,and the structures are confirmed by 1H NMR and MS.These compounds are tested in vitro for their antifungal activity by the micro-liquid-based dilution method.The results showed that the target compounds have good in vitro inhibitory activity against all strains except Aspergillus fumigatus,especially Candida albicans.Compounds[STHZ]4,9[STBZ],and[STHZ]15[STBZ]have good antifungal activity,especially compound[STHZ]15[STBZ],whose MIC 80 values are less than 0.5μg/mL for all strains except Aspergillus fumigatus.

关 键 词：氮唑类衍生物 1 3 4-噻二唑 合成 体外抗真菌活性 

分 类 号：R914.5[医药卫生—药物化学]