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

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.