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Trisubstituted Imidazoles as Mycobacterium tuberculosis Glutamine Synthetase Inhibitors

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journal contribution
posted on 2015-12-16, 21:11 authored by Johan Gising, Mikael T. Nilsson, Luke R. Odell, Samir Yahiaoui, Martin Lindh, Harini Iyer, Achyut M. Sinha, Bachally R. Srinivasa, Mats Larhed, Sherry L. Mowbray, Anders Karlén
Mycobacterium 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 IC50 values and promising antituberculosis MIC values.

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