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Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design.

ABSTRACT: The ATPase subunit of DNA gyrase B is an attractive antibacterial target due to high conservation across bacteria and the essential role it plays in DNA replication. A novel class of pyrazolopyridone inhibitors was discovered by optimizing a fragment screening hit scaffold using structure guided design. These inhibitors show potent Gram-positive antibacterial activity and low resistance incidence against clinically important pathogens.

SUBMITTER: Cross JB

PROVIDER: S-EPMC4834655 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design.

Cross Jason B JB Zhang Jing J Yang Qingyi Q Mesleh Michael F MF Romero Jan Antoinette C JA Wang Bin B Bevan Doug D Poutsiaka Katherine M KM Epie Felix F Moy Terence T Daniel Anu A Shotwell Joseph J Chamberlain Brian B Carter Nicole N Andersen Ole O Barker John J Ryan M Dominic MD Metcalf Chester A CA Silverman Jared J Nguyen Kien K Lippa Blaise B Dolle Roland E RE

ACS medicinal chemistry letters 20160216 4

The ATPase subunit of DNA gyrase B is an attractive antibacterial target due to high conservation across bacteria and the essential role it plays in DNA replication. A novel class of pyrazolopyridone inhibitors was discovered by optimizing a fragment screening hit scaffold using structure guided design. These inhibitors show potent Gram-positive antibacterial activity and low resistance incidence against clinically important pathogens. ...[more]

PMID: 27096044

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