Literature

Abstract

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile. In vivo proof of concept was achieved in a A. baumannii mouse thigh infection model.

DOI： 10.1016/j.bmcl.2022.128648

Discovery and structure–activity relationships of a novel oxazolidinone class of bacterial type II topoisomerase inhibitors

Bioorganic & Medicinal Chemistry Letters 2022.0

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

Bioorganic & Medicinal Chemistry Letters 2016.0

Synthesis and anti-staphylococcal activity of novel bacterial topoisomerase inhibitors with a 5-amino-1,3-dioxane linker moiety

Bioorganic & Medicinal Chemistry Letters 2018.0

Novel N-Linked Aminopiperidine Inhibitors of Bacterial Topoisomerase Type II with Reduced pK<sub>a</sub>: Antibacterial Agents with an Improved Safety Profile

Journal of Medicinal Chemistry 2012.0

Novel quinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV

Bioorganic & Medicinal Chemistry Letters 2013.0

Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity