合成及抗结核活性评估：还原亲脂性咪唑并[1,2-a]吡啶-3-甲酰胺衍生物。
Synthesis and antitubercular evaluation of reduced lipophilic imidazo[1,2-a]pyridine-3-carboxamide derivatives.
机构信息
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
College of Pharmacy, Southwest Minzu University, Chengdu, 610041, China.
出版信息
Eur J Med Chem. 2019 Mar 1;165:11-17. doi: 10.1016/j.ejmech.2018.12.071. Epub 2018 Dec 28.
A series of reduced lipophilic N-benzylic imidazo[1,2-a]pyridine carboxamides (IPAs) with various side chains were designed and synthesized as new anti-TB agents in this work. Five derivatives A2, A3, A4, B1 and B9 exhibit excellent in vitro activity (MIC: < 0.035 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains, and acceptable PK properties. Compound B1 bearing a cyclohexylmethyl piperazine moiety, the same side chain of PBTZ169, was found to have obviously greater AUC and C than Q203 and PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
本工作设计并合成了一系列具有不同侧链的脂溶性降低的 N-苄基咪唑并[1,2-a]吡啶甲酰胺（IPAs），作为新型抗结核药物。衍生物 A2、A3、A4、B1 和 B9 对药敏结核分枝杆菌 H37Rv 株和两种临床分离的耐多药菌株均表现出优异的体外活性（MIC：<0.035 μM），且具有可接受的 PK 性质。具有环己基甲基哌嗪部分的化合物 B1 与 PBTZ169 的相同侧链，其 AUC 和 C 明显大于 Q203 和 PBTZ169，表明其具有成为未来抗结核药物发现的潜在先导化合物的潜力。
Zotero 插件