Trisubstituted Imidazoles as Mycobacterium tuberculosis Glutamine Synthetase Inhibitors
2012; American Chemical Society; Volume: 55; Issue: 6 Linguagem: Inglês
10.1021/jm201212h
ISSN1520-4804
AutoresJohan Gising, Mikael Nilsson, Luke R. Odell, Samir Yahiaoui, Martin Lindh, Harini Iyer, A M Sinha, B. R. Srinivasa, Mats Larhed, Sherry L. Mowbray, Anders Karlén,
Tópico(s)Tuberculosis Research and Epidemiology
ResumoMycobacterium tuberculosis glutamine synthetase (MtGS) is a promising target for antituberculosis drug discovery. In a recent high-throughput screening study we identified several classes of MtGS inhibitors targeting the ATP-binding site. We now explore one of these classes, the 2-tert-butyl-4,5-diarylimidazoles, and present the design, synthesis, and X-ray crystallographic studies leading to the identification of MtGS inhibitors with submicromolar IC(50) values and promising antituberculosis MIC values.
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