咪唑并[2,1-b]噻唑-5-甲酰胺类化合物的设计、合成与体外抗结核活性  

New imidazo[2,1-b]thiazole-5-carboxamides:design,synthesis and antitubercular activity

作　　者：杨帆 李林虎[2,3] 吕凯 刘明亮[2] 汪阿鹏[2] YANG Fan;LI Lin-hu;LYU Kai;LIU Ming-liang;WANG A-peng(The Third Affiliated Hospital of Naval Medical University,Shanghai 201805,China;Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;Limin Chemical Co.,Ltd.,Xinyi 221422,China)

机构地区：[1]海军军医大学第三附属医院,上海201805 [2]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [3]利民化学有限责任公司,江苏新沂221422

出　　处：《中国医药生物技术》2022年第3期201-206,共6页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(81872753、81903477)。

摘　　要：目的设计合成一系列咪唑并[2,1-b]噻唑-5-甲酰胺类化合物,并评价其体外抗结核杆菌(MTB)活性。方法关键中间体与母核化合物通过缩合反应制备目标物,其结构经1H-NMR、13C-NMR和MS确证。MABA法测定所有目标物及对照药对MTBH37Rv和MDR-MTB的MIC值。结果合成了30个咪唑并[2,1-b]噻唑-5-甲酰胺类化合物(包括先导物A)。部分目标物对两株MTB均敏感(MIC<0.016~0.211μg/ml),其中1e的体外活性与Q203相当,而优于先导物A。结论丰富了咪唑并[2,1-b]噻唑-5-甲酰胺类化合物抗结核构效关系,为下一步相关研究奠定了基础。Objective We aim to design and synthesize a series of new imidazo[2,1-b]thiazole-5-carboxamides,and evaluate their in vitro antitubercular activity.Methods Target compounds were synthesized through condensation of key intermediates with imidazo[2,1-b]thiazole-5-carboxamide cores.Their structures were characterized by 1H-NMR,13C-NMR and MS.In vitro antitubercular activity of the compounds were evaluated by MABA assay.Results Thirty compounds including the lead compound A were synthesized in this study.Some of them were found to be active against both the two MTB strains(MIC<0.016-0.211μg/ml),and compound 1 e was more active than the lead compound A and comparable to Q203.Conclusion This study enriches the structure activity relationship information of imidazo[2,1-b]thiazole-5-carboxamides against MTB,which lays the foundation for the future research.

关 键 词：咪唑并[2 1-b]噻唑-5-甲酰胺类化合物 合成 抗结核活性 构效关系 

分 类 号：R914.5[医药卫生—药物化学]