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

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 des...

Full description

Saved in:
Bibliographic Details
Published inACS medicinal chemistry letters Vol. 7; no. 4; pp. 374 - 378
Main Authors Cross, Jason B, Zhang, Jing, Yang, Qingyi, Mesleh, Michael F, Romero, Jan Antoinette C, Wang, Bin, Bevan, Doug, Poutsiaka, Katherine M, Epie, Felix, Moy, Terence, Daniel, Anu, Shotwell, Joseph, Chamberlain, Brian, Carter, Nicole, Andersen, Ole, Barker, John, Ryan, M. Dominic, Metcalf, Chester A, Silverman, Jared, Nguyen, Kien, Lippa, Blaise, Dolle, Roland E
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 14.04.2016
Amer Chemical Soc
Subjects
Chemistry, Medicinal
Letter
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
structure-based drug design
fragment-based drug design
Antibacterials
DNA gyrase B
LEAD DISCOVERY
GYRB
MECHANISM
POTENT
ANTIBACTERIAL ACTIVITY
DNA GYRASE
AGENTS
OPTIMIZATION
SCAFFOLD
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.5b00368