Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

被引：10

作者：

Cooper, Ian R. ^{[1
]}

McCarroll, Andrew J. ^{[1
]}

McGarry, David ^{[1
]}

Kirkham, James ^{[1
]}

Pichowicz, Mark ^{[1
]}

Walker, Rolf ^{[1
]}

Warrilow, Catherine ^{[1
]}

Salisbury, Anne-Marie ^{[1
]}

Savage, Victoria J. ^{[1
]}

Moyo, Emmanuel ^{[1
]}

Forward, Henry ^{[1
]}

Cheung, Jonathan ^{[1
]}

Metzger, Richard ^{[1
]}

Gault, Zoe ^{[1
]}

Nelson, Gary ^{[1
]}

Hughes, Diarmaid ^{[2
]}

Cao, Sha ^{[2
]}

Maclean, John ^{[1
]}

Charrier, Cedric ^{[1
]}

Craighead, Mark ^{[1
]}

Best, Stuart ^{[1
]}

Stokes, Neil R. ^{[1
]}

Ratcliffe, Andrew J. ^{[1
]}

机构：

[1] Redx Pharma, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[2] Uppsala Univ, Dept Med Biochem & Microbiol, Box 582 Biomed Ctr, Uppsala, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 17期

关键词：

ESKAPE pathogens; Anti-infectives; Topoisomerases; DNA gyrase; Isothiazolone; FLUOROQUINOLONE RESISTANCE; IN-VITRO; PATHOGENS; MECHANISMS; INFECTIONS; AGENTS;

D O I：

10.1016/j.bmcl.2016.07.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4179 / 4183

页数：5

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