Wang Apeng, Huang Guocheng, Wang Bin, Lv Kai, Wang Hongjian, Tao Zeyu, Liu Mingliang, Guo Huiyuan, Lu Yu
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
Bioorg Med Chem Lett. 2018 Sep 15;28(17):2945-2948. doi: 10.1016/j.bmcl.2018.07.005. Epub 2018 Jul 7.
We report herein the design, synthesis and antimycobacterial activity of 3,5-dinitrobenzamide derivatives containing fused ring moieties. Results reveal that many of the target compounds have considerable in vitro antitubercular activity. Especially, N-((2-(4-fluorophenyl)/N-((2-(3-fluorobenzyl)-1,2,3,4-tetrahydroisoquilin-6-yl)methyl)-3,5-dinitrobenzamides 18a and 20e exhibit potent MIC values of 0.056-0.078 μg/mL against both drug-sensitive Mycobacterium tuberculosis (MTB) H37Rv strain and two clinically isolated multidrug-resistant MTB (MDR-MTB) strains, opening a new direction for further SAR studies.
本文报道了含稠环部分的3,5-二硝基苯甲酰胺衍生物的设计、合成及抗分枝杆菌活性。结果表明，许多目标化合物具有相当的体外抗结核活性。特别是，N-((2-(4-氟苯基)/N-((2-(3-氟苄基)-1,2,3,4-四氢异喹啉-6-基)甲基)-3,5-二硝基苯甲酰胺18a和20e对药物敏感的结核分枝杆菌（MTB）H37Rv菌株和两株临床分离的耐多药MTB（MDR-MTB）菌株表现出0.056 - 0.078μg/mL的强效最低抑菌浓度值，为进一步的构效关系研究开辟了新方向。
