Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives

被引：31

作者：

Lv, Kai ^{[1
,2
]}

Li, Linhu ^{[1
,2
]}

Wang, Bo ^{[1
,2
]}

Liu, Mingliang ^{[1
,2
]}

Wang, Bin ^{[3
]}

Shen, Weiyi ^{[4
]}

Guo, Huiyuan ^{[1
,2
]}

Lu, Yu ^{[3
]}

机构：

[1] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Capital Med Univ, Beijing TB & Thorac Tumor Res Inst, Beijing Key Lab Drug Resistance TB Res, Dept Pharmacol,Beijing ChestHosp, Beijing 101149, Peoples R China

[4] Zhejiang Starry Pharmaceut Co Ltd, Xianju 317300, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 137卷

关键词：

Imidazo[1,2-a]pyridine; Design; Synthesis; Antimycobacterial activity; RESISTANT MYCOBACTERIUM-TUBERCULOSIS; CLINICAL CANDIDATE; AGENTS; Q203;

D O I：

10.1016/j.ejmech.2017.05.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report herein the design and synthesis of "novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)" bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041-2.64 mu M) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：117 / 125

页数：9

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