Imidazopyridines or Fused Imidazoles for Anti-TB 2016

Identification of N-(2-Phenoxyethyl)imidazo[1,2-a]pyridine-3-carboxamides as New Antituberculosis Agents

Zhaoyang Wu^†⊥, Yu Lu^‡⊥, Linhu Li^†, Rui Zhao^†, Bin Wang^‡, Kai Lv^†§, Mingliang Liu^*†, and Xuefu You^*†

^† 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

^§ Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States

ACS Med. Chem. Lett., Article ASAP

DOI: 10.1021/acsmedchemlett.6b00330

Publication Date (Web): October 11, 2016

Copyright © 2016 American Chemical Society

*Tel: 010-63030965. Fax: 010-63036965. E-mail: lmllyx@126.com., *E-mail: xuefuyou116@yahoo.cn.

Abstract

 

 

A series of imidazo[1,2-a]pyridine carboxamides (IPAs) bearing an N-(2-phenoxyethyl) moiety

was designed and synthesized as new antitubercular agents. Seven 2,6-dimethyl IPAs demonstrated excellent in vitro activity (MIC: 0.025–0.054 μg/mL) against the drug susceptive H37Rv strain and two clinically isolated multidrug-resistant Mycobacterium tuberculosisstrains. Compound 10j displayed acceptable safety and pharmacokinetic properties, opening a new direction for further development.

Keywords:

Antitubercular agents; MTB H37Rv; multidrug resistant-MTB; N-(2-phenoxyethyl)imidazo[1,2-a]pyridine carboxamides; structure−activity relationship

Supporting Information

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmedchemlett.6b00330.

• Experimental procedures and analytical data for compounds 10a–m, 11a–n, and 14 (PDF)

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