论文题目：Design, Synthesis, and Evaluation of Substituted 2-acylamide-1,3-benzo[d]zole Analogues as Agents against MDR- and XDR-MTB

作者：Dongsheng Li, Chao Liu, Xinhai Jiang, Yuan Lin, Jing Zhang, Yan Li, Xuefu You, Wei Jiang, Minghua Chen., Yanni Xu, Shuyi Si

期刊名称：Eur J Med Chem

IF：5.572

年份：2021

卷期页：209:112898

N-(5-Chlorobenzo[d]oxazol-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamideox-amide has been identified as a potent inhibitor of Mtb H37Rv, with a minimum inhibitory concentration (MIC) of 0.42 μM. In this study, a series of substituted 2-acylamide-1,3-zole analogues were designed and synthesized, and their anti-Mtb activities were analyzed. In total, 17 compounds were found to be potent anti-Mtb agents, especially against the MDR- and XDR-MTB strains, with MIC values < 10 μM. These analogues can inhibit both drug-sensitive and drug-resistant Mtb. Four representative compounds were selected for further profiling, and the results indicate that compound 18 is acceptably safe and has favorable pharmacokinetic (PK) properties. In addition, this compound displays potent activity against Gram-positive bacteria, with MIC values in the range of 1.48-11.86 μM. The data obtained herein suggest that promising anti-Mtb candidates may be developed via structural modification, and that further research is needed to explore other compounds.