Discovery of Indazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors

Jing Zhang, Qingyi Yang, Jan Antoinette C. Romero, Jason Cross, Bin Wang, Katherine M. Poutsiaka, Felix Epie, Douglas Bevan, Yuchuan Wu, Terence Moy, Anu Daniel, Brian Chamberlain, Nicole Carter, Joseph Shotwell, Anu Arya, Vipul Kumar, Jared Silverman, Kien Nguyen, Chester A. Metcalf, Dominic RyanBlaise Lippa, Roland E. Dolle

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Antibacterials with a novel mechanism of action offer a great opportunity to combat widespread antimicrobial resistance. Bacterial DNA Gyrase is a clinically validated target. Through physiochemical property optimization of a pyrazolopyridone hit, a novel class of GyrB inhibitors were discovered. Guided by structure-based drug design, indazole derivatives with excellent enzymatic and antibacterial activity as well as great animal efficacy were discovered.

Original languageEnglish
Pages (from-to)1080-1085
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume6
Issue number10
DOIs
StatePublished - Oct 8 2015
Externally publishedYes

Keywords

  • Antibacterial
  • GyrB
  • MRSA
  • indazole
  • topoisomerase

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  • Cite this

    Zhang, J., Yang, Q., Romero, J. A. C., Cross, J., Wang, B., Poutsiaka, K. M., Epie, F., Bevan, D., Wu, Y., Moy, T., Daniel, A., Chamberlain, B., Carter, N., Shotwell, J., Arya, A., Kumar, V., Silverman, J., Nguyen, K., Metcalf, C. A., ... Dolle, R. E. (2015). Discovery of Indazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors. ACS Medicinal Chemistry Letters, 6(10), 1080-1085. https://doi.org/10.1021/acsmedchemlett.5b00266