Discovery of Azaindole Ureas as a Novel Class of Bacterial Gyrase B Inhibitors

详细信息    查看全文

• 作者：Jing Zhang ; Qingyi Yang ; Jason B. Cross ; Jan Antoinette C. Romero ; Katherine M. Poutsiaka ; Felix Epie ; Douglas Bevan ; Bin Wang ; Yanzhi Zhang ; Ajit Chavan ; Xin Zhang ; Terence Moy ; Anu Daniel ; Kien Nguyen ; Brian Chamberlain ; Nicole Carter ; Joseph Shotwell ; Jared Silverman ; Chester A. Metcalf III ; Dominic Ryan ; Blaise Lippa ; Roland E. Dolle
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：November 12, 2015
• 年：2015
• 卷：58
• 期：21
• 页码：8503-8512
• 全文大小：535K
• ISSN：1520-4804

文摘

The emergence and spread of multidrug resistant bacteria are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the discovery of azaindole ureas as a novel class of bacterial gyrase B inhibitors and detail the story of their evolution from a de novo design hit based on structure-based drug design. These inhibitors show potent minimum inhibitory concentrations against fluoroquinolone resistant MRSA and other Gram-positive bacteria.