新型氮唑衍生物的合成及体外抗真菌活性  

Novel Azole Derivatives and Antifungal Activities in vitro

作　　者：梁伦海 刘丽 张胜男 孟庆国[1] 赵风兰[1] 柴晓云 LIANG Lun-hai;LIU Li;ZHANG Sheng-nan;MENG Qing-guo;ZHAO Feng-lan;CHAI Xiao-yun(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China;School of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[1]烟台大学药学院,分子药理和药物评价教育部重点实验室(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,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）》2022年第1期35-41,共7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(2020XDRH105)。

摘　　要：以伊曲康唑中间体1为底物,经叠氮化钠亲核取代、氨基还原和缩合反应,合成19个伊曲康唑衍生物,并用于抗真菌构效关系研究,经文献检索,所合成的化合物均为新化合物,且均经^(1)H NMR和MS确证。通过最小抑制浓度(MICs)评估化合物体外抗真菌活性,结果显示伊曲康唑衍生物对白念珠菌和近平滑假丝酵母菌均具有较好的体外抑制活性,衍生物A5、A6、A10和A14对除烟曲霉菌外的测试菌株均具有较好的体外抑制活性,特别是衍生物A6,具有进一步的研究价值。Using itraconazole intermediate1 as substrate,19 itraconazole derivatives are synthesized by nucleophilic substitution,reduction and condensation reaction.All the synthesized compounds are used for antifungal structural-activity relationship study.The literature search proves that the synthesized compounds are all new compounds.All structures are confirmed by ^(1)H NMR and MS.The minimum inhibitory concentrations(MICs)evaluation for in vitro antifungal activity shows that all the itraconazole derivatives had good inhibitory activity in vitro to the tested strains.Among these,derivatives A5,A6,A10 and A14 have better inhibitory activity in vitro to all the strains except aspergillus fumigates,in particular,the derivative A6 has further research value.

关 键 词：氮唑 合成 构效关系 抗真菌活性 

分 类 号：R914.5[医药卫生—药物化学]