Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E-coli

被引：28

作者：

Aberg, Veronica ^{[1
]}

Das, Pralay ^{[1
]}

Chorell, Erik ^{[1
]}

Hedenstrom, Mattias ^{[1
]}

Pinkner, Jerome S. ^{[2
]}

Hultgren, Scott J. ^{[2
]}

Almqvist, Fredrik ^{[1
]}

机构：

[1] Umea Univ, Dept Chem, SE-90187 Umea, Sweden

[2] Washington Univ, St Louis Sch Med, St Louis, MO 63110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 12期

关键词：

2-pyridone; bioisostere; antimicrobial; pili; Escherichia coli; pilicide;

D O I：

10.1016/j.bmcl.2008.05.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic Escherichia coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here, we present the synthesis and biological evaluation of carboxylic acid isosteres, including, for example, tetrazoles, acyl sulfonamides, and hydroxamic acids of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli. (C) 2008 Elsevier Ltd. All rights reserved.

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页码：3536 / 3540

页数：5

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