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

被引：40

作者：

Cross, Jason B. ^{[1
]}

Zhang, Jing ^{[1
]}

Yang, Qingyi ^{[1
]}

Mesleh, Michael F. ^{[1
]}

Romero, Jan Antoinette C. ^{[1
]}

Wang, Bin ^{[1
]}

Bevan, Doug ^{[1
]}

Poutsiaka, Katherine M. ^{[1
]}

Epie, Felix ^{[1
]}

Moy, Terence ^{[1
]}

Daniel, Anu ^{[1
]}

Shotwell, Joseph ^{[1
]}

Chamberlain, Brian ^{[1
]}

Carter, Nicole ^{[1
]}

Andersen, Ole ^{[2
]}

Barker, John ^{[2
]}

Ryan, M. Dominic ^{[1
]}

Metcalf, Chester A., III ^{[1
]}

Silverman, Jared ^{[1
]}

Nguyen, Kien ^{[1
]}

Lippa, Blaise ^{[1
]}

Dolle, Roland E. ^{[1
]}

机构：

[1] Cubist Pharmaceut Inc, 65 Hayden Ave, Lexington, MA 02421 USA

[2] Evotec UK Ltd, 114 Innovat Dr,Milton Pk, Abingdon OX14 4RZ, Oxon, England

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 04期

关键词：

Antibacterials; DNA gyrase B; fragment-based drug design; structure-based drug design; DNA GYRASE; ANTIBACTERIAL ACTIVITY; LEAD DISCOVERY; AGENTS; GYRB; OPTIMIZATION; MECHANISM; SCAFFOLD; POTENT;

D O I：

10.1021/acsmedchemlett.5b00368

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：374 / 378

页数：5

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