title: Functionalized 3-amino-imidazo[1,2-a]pyridines: a novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors.
abstract: 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 (IC(50)=0.38+/-0.02 microM). This compound was significantly more potent than the known inhibitors, l-methionine-SR-sulfoximine and phosphinothricin.
authors: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Biomedical Center, SE-751 23 Uppsala, Sweden.
authors: Luke R
authors: LR
authors: Odell
authors: Mikael T
authors: MT
authors: Nilsson
authors: Johan
authors: J
authors: Gising
authors: Olof
authors: O
authors: Lagerlund
authors: Daniel
authors: D
authors: Muthas
authors: Anneli
authors: A
authors: Nordqvist
authors: Anders
authors: A
authors: Karlén
authors: Mats
authors: M
authors: Larhed
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C543972:3-amino-imidazo(1,2-a)pyridine; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D005974:Glutamate-Ammonia Ligase