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

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, Jared Silverman, Kien NguyenBlaise Lippa, Roland E. Dolle

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)374-378
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume7
Issue number4
DOIs
StatePublished - Apr 14 2016

Keywords

  • Antibacterials
  • DNA gyrase B
  • fragment-based drug design
  • structure-based drug design

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