设计、合成和生物评价硝基呋喃-1,3,4-噁二唑杂合体作为新型抗结核药物。
Design, synthesis and biological evaluation of nitrofuran-1,3,4-oxadiazole hybrids as new antitubercular agents.
机构信息
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
出版信息
Bioorg Med Chem. 2022 Jan 1;53:116529. doi: 10.1016/j.bmc.2021.116529. Epub 2021 Nov 25.
Three series of novel nitrofuran-1,3,4-oxadiazole hybrids were designed and synthesized as new anti-TB agents. The structure activity relationship study indicated that the linkers and the substituents on the oxadiazole moiety greatly influence the activity, and the substituted benzenes are more favoured than the cycloalkyl or heterocyclic groups. Besides, the optimal compound in series 2 was active against both MTB HRv strain and MDR-MTB 16883 clinical isolate and also displayed low cytotoxicity, low inhibition of hERG and good oral PK, indicating its promising potential to be a lead for further structural modifications.
设计并合成了三系列新型硝呋喃-1,3,4-噁二唑杂合体，作为新型抗结核药物。构效关系研究表明，噁二唑部分的连接基团和取代基对活性影响较大，取代苯比环烷基或杂环基团更有利。此外，系列 2 中的最佳化合物对 HRv 结核分枝杆菌菌株和 16883 临床分离的耐多药结核分枝杆菌均具有活性，并且还显示出低细胞毒性、低 hERG 抑制作用和良好的口服 PK，表明其具有进一步结构修饰的潜在前景。
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