Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity
Yule, IA, Czaplewski, LG, Pommier, S et al. (3 more authors)
(2014)
Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity.
European Journal of Medicinal Chemistry, 86.
31 - 38.
ISSN 0223-5234
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.
Metadata
Authors/Creators:
Yule, IA
Czaplewski, LG
Pommier, S
Davies, DT
Narramore, SK
Fishwick, CWG
Copyright, Publisher and Additional Information:
(c) 2014, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in the European Journal of Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in European Journal of Medicinal Chemistry, 86, 2014, 10.1016/j.ejmech.2014.08.025
Keywords:
Bacterial resistance; DNA gyrase; pyridine-3-carboxamide; molecular modelling
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CORE (COnnecting REpositories)