1. Academic Validation
  2. Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

  • Bioorg Med Chem Lett. 2016 Sep 1;26(17):4179-83. doi: 10.1016/j.bmcl.2016.07.061.
Ian R Cooper 1 Andrew J McCarroll 2 David McGarry 2 James Kirkham 2 Mark Pichowicz 2 Rolf Walker 2 Catherine Warrilow 2 Anne-Marie Salisbury 2 Victoria J Savage 2 Emmanuel Moyo 2 Henry Forward 2 Jonathan Cheung 2 Richard Metzger 2 Zoe Gault 2 Gary Nelson 2 Diarmaid Hughes 3 Sha Cao 3 John Maclean 2 Cédric Charrier 2 Mark Craighead 2 Stuart Best 2 Neil R Stokes 2 Andrew J Ratcliffe 2
Affiliations

Affiliations

  • 1 Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom. Electronic address: i.cooper@redxpharma.com.
  • 2 Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom.
  • 3 Department of Medical Biochemistry and Microbiology, Box 582 Biomedical Center, Uppsala University, Uppsala, Sweden.
Abstract

There is an urgent and unmet medical need for new Antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of Bacterial type II Topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.

Keywords

Anti-infectives; DNA gyrase; ESKAPE pathogens; Isothiazolone; Topoisomerases.

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