Discovery of novel N-phenylphenoxyacetamide derivatives as EthR inhibitors and ethionamide boosters by combining high-throughput screening and synthesis

…, N Lecat-Guillet, C Hounsou, M Desroses…

Index: Flipo, Marion; Willand, Nicolas; Lecat-Guillet, Nathalie; Hounsou, Candide; Desroses, Matthieu; Leroux, Florence; Lens, Zoe; Villeret, Vincent; Wohlkoenig, Alexandre; Wintjens, Rene; Christophe, Thierry; Kyoung Jeon, Hee; Locht, Camille; Brodin, Priscille; Baulard, Alain R; Deprez, Benoit Journal of Medicinal Chemistry, 2012 , vol. 55, # 14 p. 6391 - 6402

Full Text: HTML

Citation Number: 17

Abstract

In this paper, we describe the screening of a 14640-compound library using a novel whole mycobacteria phenotypic assay to discover inhibitors of EthR, a transcriptional repressor implicated in the innate resistance of Mycobacterium tuberculosis to the second-line antituberculosis drug ethionamide. From this screening a new chemical family of EthR inhibitors bearing an N-phenylphenoxyacetamide motif was identified. The X-ray structure ...