DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: Synthesis and antibacterial activity

East, Stephen P.; White, Clara Bantry; Barker, Oliver; Barker, Stephanie; Bennett, James M.; Brown, David G.; Boyd, E. Andrew; Brennan, Christopher M.; Chowdhury, Chandana; Collins, Ian; Convers-Reignier, Emmanuelle; Dymock, Brian; Fletcher, Rowena; Haydon, David J.; Gardiner, Mihaly; Hatcher, Stuart; Ingram, P. L.; Lancett, Paul; Mortenson, Paul N.; Papadopoulos, Konstantinos; Smee, C.; Thomaides-Brears, Helena; Tye, Heather; Workman, James; Czaplewski, Lloyd G.

doi:10.1016/j.bmcl.2008.11.102

Cited by 70 publications

(49 citation statements)

References 14 publications

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“…To test the modelling hypothesis, compound 7 was prepared according to the procedure described in Scheme 1 from commercially available 6-aminonicotinate 8. c data from Starr et al [10]; d data from East et al [8] As indicated from inspection of the data in Table 1, although compound 7 synthesised as part of the present work was 1 -2 orders of magnitude less potent against GyrB than those previously reported, this was encouraging given the lower molecular weight / complexity of this inhibitor. Furthermore, the antimicrobial activity found for this compound, albeit weak, indicated the potential for optimisation.…”

Section: Synthesis Of Putative Inhibitorssupporting

confidence: 66%

“…[6] More recently, the development of small molecule ATPase inhibitors of gyrase (GyrB) and topo IV (ParE), aided by the elucidation of proteinligand structures of GyrB, has gained attention as a means to inhibit these classical enzyme targets in the pursuit of novel antibacterial compounds. [7][8][9][10] Encouraged by these reports, our interest in the discovery of novel ATPase inhibitors of GyrB / ParE began with the observation that a number of reports in the literature demonstrated that heterocyclic N-ethylurea derivatives to be conducive with potent dualinhibitory ATPase activity coupled to antimicrobial activity. [7,8,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10] Encouraged by these reports, our interest in the discovery of novel ATPase inhibitors of GyrB / ParE began with the observation that a number of reports in the literature demonstrated that heterocyclic N-ethylurea derivatives to be conducive with potent dualinhibitory ATPase activity coupled to antimicrobial activity. [7,8,10,11]. Notably, benzimidazol-2-yl-ureas (1), benzathiazol-2-yl-ureas (2), imidazopyridin-2-yl-ureas (3), triazolopyridine-5-carboxamides (4), isoquinolin-3-yl-ureas (5) and pyridin-3-yl-ureas (6) reported by groups at Vertex [7], Prolysis 11 , Pfizer [10], Evotec [8], Actelion [12] and AstraZeneca [13] respectively, exemplify the prevalence of this moiety amongst antibacterial GyrB / ParE inhibitors ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…[7,8,10,11]. Notably, benzimidazol-2-yl-ureas (1), benzathiazol-2-yl-ureas (2), imidazopyridin-2-yl-ureas (3), triazolopyridine-5-carboxamides (4), isoquinolin-3-yl-ureas (5) and pyridin-3-yl-ureas (6) reported by groups at Vertex [7], Prolysis 11 , Pfizer [10], Evotec [8], Actelion [12] and AstraZeneca [13] respectively, exemplify the prevalence of this moiety amongst antibacterial GyrB / ParE inhibitors ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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

Yule

Czaplewski²,

Pommier³

et al. 2014

European Journal of Medicinal Chemistry

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This is a repository copy of ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity.

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Section: Synthesis Of Putative Inhibitorssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yule

Czaplewski²,

Pommier³

et al. 2014

European Journal of Medicinal Chemistry

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“…They also act through inhibition of GyrB/ParE. They present activity mostly against Gram-positive bacteria (MSSA, MRSA, S. pneumoniae) [52].…”

Section: Fluoroquinolones and Compounds With Anti-gyrase/topoisomerasmentioning

confidence: 99%

New perspectives on antibacterial drug research

2013

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Bacterial resistance to commonly used antibiotics is constantly increasing. Bacteria particularly dangerous for human life are methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and fluoroquinolone-resistant Pseudomonas aeruginosa. Hence, there is an incessant need for developing compounds with new modes of action and seeking alternate drug targets. In this review, the authors discuss the current situation of antibacterial medicines and present data on new antibiotic targets. Moreover, alternatives to antibiotics, such as bacteriophages, antimicrobial peptides and monoclonal antibodies, are presented. The authors also draw attention to the valuable features of natural sources in developing antibacterial compounds. The need to prevent and control infections as well as the reasonable use of currently available antibiotics is also emphasized.

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Polypharmacology as an Emerging Trend in Antibacterial Discovery

Silver¹

2012

Polypharmacology in Drug Discovery

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DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: Synthesis and antibacterial activity

Cited by 70 publications

References 14 publications

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

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

New perspectives on antibacterial drug research

Polypharmacology as an Emerging Trend in Antibacterial Discovery

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