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

被引：88

作者：

Odell, Luke R. ^{[1
]}

Nilsson, Mikael T. ^{[2
]}

Gising, Johan ^{[1
]}

Lagerlund, Olof ^{[1
]}

Muthas, Daniel ^{[1
]}

Nordqvist, Anneli ^{[1
]}

Karlen, Anders ^{[1
]}

Larhed, Mats ^{[1
]}

机构：

[1] Uppsala Univ, Biomed Ctr, Dept Med Chem, SE-75123 Uppsala, Sweden

[2] Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 16期

基金：

瑞典研究理事会;

关键词：

Mycobacterium tuberculosis; Glutamine synthetase inhibitors; Microwave; 3-Aminoimidazo[1,2-a]pyridine; CROSS-COUPLING REACTIONS; SOLID-PHASE SYNTHESIS; 3-COMPONENT CONDENSATION; PHOSPHINOTHRICIN; PYRAZINES; ANALOGS; TARGETS; DESIGN; ENZYME;

D O I：

10.1016/j.bmcl.2009.06.045

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M). This compound was significantly more potent than the known inhibitors, L-methionine-SR-sulfoximine and phosphinothricin. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4790 / 4793

页数：4

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