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Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors.

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.

SUBMITTER: Gising J

PROVIDER: S-EPMC3381009 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors.

Gising Johan J Nilsson Mikael T MT Odell Luke R LR Yahiaoui Samir S Lindh Martin M Iyer Harini H Sinha Achyut M AM Srinivasa Bachally R BR Larhed Mats M Mowbray Sherry L SL Karlén Anders A

Journal of medicinal chemistry 20120308 6

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 MI ...[more]

PMID: 22369127

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