Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors.
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Gising J, Nilsson MT, Odell LR, Yahiaoui S, Lindh M, Iyer H, Sinha AM, Srinivasa BR, Larhed M, Mowbray SL, Karlen A
Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors.
J Med Chem. 2012 Mar 22;55(6):2894-8. doi: 10.1021/jm201212h. Epub 2012 Mar 8.
- PubMed ID
- 22369127 [ View in PubMed]
- Abstract
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 IC(50) values and promising antituberculosis MIC values.