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

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• 作者：Jason B. Cross ; Jing Zhang ; Qingyi Yang ; Michael F. Mesleh ; Jan Antoinette C. Romero ; Bin Wang ; Doug Bevan ; Katherine M. Poutsiaka ; Felix Epie ; Terence Moy ; Anu Daniel ; Joseph Shotwell ; Brian Chamberlain ; Nicole Carter ; Ole Andersen ; John Barker ; M. Dominic Ryan ; Chester A. Metcalf III ; Jared Silverman ; Kien Nguyen ; Blaise Lippa ; Roland E. Dolle
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：April 14, 2016
• 年：2016
• 卷：7
• 期：4
• 页码：374-378
• 全文大小：398K
• 年卷期：0
• ISSN：1948-5875

文摘

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.