Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity

被引：49

作者：

Yule, Ian A. ^{[1
]}

Czaplewski, Lloyd G. ^{[2
]}

Pommier, Stephanie ^{[2
]}

Davies, David T. ^{[2
]}

Narramore, Sarah K. ^{[1
]}

Fishwick, Colin W. G. ^{[1
]}

机构：

[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

[2] Biota Europe Ltd, Begbroke OX5 1PF, Oxon, England

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 86卷

基金：

英国工程与自然科学研究理事会;

关键词：

Bacterial resistance; DNA gyrase; Pyridine-3-carboxamide; Molecular modelling; TOPOISOMERASE-IV; ANTIBACTERIAL AGENTS; UREA INHIBITORS; NO ESKAPE; RESISTANCE; DISCOVERY; DRUGS; PARE;

D O I：

10.1016/j.ejmech.2014.08.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram positive antibacterial efficacy. (c) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：31 / 38

页数：8

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