Trisubstituted Imidazoles as Mycobacterium tuberculosis Glutamine Synthetase Inhibitors

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• 作者：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 Karl茅n
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 22, 2012
• 年：2012
• 卷：55
• 期：6
• 页码：2894-2898
• 全文大小：276K
• 年卷期：v.55,no.6(March 22, 2012)
• ISSN：1520-4804

文摘

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.