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.
- 1. Redx Pharma, Alderley Park, Cheshire SK10 4TG, United Kingdom. Electronic address: [email protected].
- 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.
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.