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; Xuefu You

doi:10.1021/acsmedchemlett.6b00330

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

ACS Med Chem Lett. 2016 Oct 11;7(12):1130-1133. doi: 10.1021/acsmedchemlett.6b00330. eCollection 2016 Dec 8.

Authors

Zhaoyang Wu¹, Yu Lu², Linhu Li¹, Rui Zhao¹, Bin Wang², Kai Lv³, Mingliang Liu¹, Xuefu You¹

Affiliations

¹ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050, China.
² 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.
³ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States.

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