Functionalized 3-amino-imidazo[1,2-a]pyridines: A novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors

3-Amino-imidazo[1,2-a]pyridines have been identified as a novel class of Mycobacterium tuberculosis glutamine synthetase inhibitors. Moreover, these compounds represent the first drug-like inhibitors of this enzyme. A series of compounds exploring structural diversity in the pyridine and phenyl rings have been synthesized and biologically evaluated. Compound 4n was found to be the most potent inhibitor (IC50 = 0.38 ± 0.02 μM). This compound was significantly more potent than the known inhibitors, l-methionine-SR-sulfoximine and phosphinothricin.

Graphical abstractFunctionalized 3-amino-imidazo[1,2-a]pyridines have been prepared and evaluated for their inhibitory activity against Mycobacterium tuberculosis glutamine synthetase. Compound 4n was found to be the most potent inhibitor with an IC50 of 0.38 ± 0.02 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide