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Discovery of Indazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors.

ABSTRACT: Antibacterials with a novel mechanism of action offer a great opportunity to combat widespread antimicrobial resistance. Bacterial DNA Gyrase is a clinically validated target. Through physiochemical property optimization of a pyrazolopyridone hit, a novel class of GyrB inhibitors were discovered. Guided by structure-based drug design, indazole derivatives with excellent enzymatic and antibacterial activity as well as great animal efficacy were discovered.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4601062 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Discovery of Indazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors.

Zhang Jing J Yang Qingyi Q Romero Jan Antoinette C JA Cross Jason J Wang Bin B Poutsiaka Katherine M KM Epie Felix F Bevan Douglas D Wu Yuchuan Y Moy Terence T Daniel Anu A Chamberlain Brian B Carter Nicole N Shotwell Joseph J Arya Anu A Kumar Vipul V Silverman Jared J Nguyen Kien K Metcalf Chester A CA Ryan Dominic D Lippa Blaise B Dolle Roland E RE

ACS medicinal chemistry letters 20150908 10

Antibacterials with a novel mechanism of action offer a great opportunity to combat widespread antimicrobial resistance. Bacterial DNA Gyrase is a clinically validated target. Through physiochemical property optimization of a pyrazolopyridone hit, a novel class of GyrB inhibitors were discovered. Guided by structure-based drug design, indazole derivatives with excellent enzymatic and antibacterial activity as well as great animal efficacy were discovered. ...[more]

PMID: 26487916

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