Abstract
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.
Keywords:
Bacterial resistance; DNA gyrase; Molecular modelling; Pyridine-3-carboxamide.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Bacteria / drug effects*
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Bacteria / enzymology
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Bacteria / metabolism
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DNA Gyrase / metabolism*
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Dose-Response Relationship, Drug
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Drug Design*
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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Topoisomerase II Inhibitors / chemical synthesis
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Topoisomerase II Inhibitors / chemistry
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Topoisomerase II Inhibitors / pharmacology*
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / chemistry
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Urea / pharmacology*
Substances
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Anti-Bacterial Agents
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Topoisomerase II Inhibitors
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Urea
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DNA Gyrase