Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2

R Kirk; A Ratcliffe; G Noonan; M Uosis-Martin; D Lyth; O Bardell-Cox; J Massam; P Schofield; A Lyons; D Clare; J Maclean; A Smith; V Savage; S Mohmed; C Charrier; A-M Salisbury; E Moyo; N Ooi; N Chalam-Judge; J Cheung; N R Stokes; S Best; M Craighead; R Armer; A Huxley

doi:10.1039/d0md00175a

Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 2

RSC Med Chem. 2020 Sep 18;11(12):1379-1385. doi: 10.1039/d0md00175a. eCollection 2020 Dec 17.

Authors

R Kirk¹, A Ratcliffe¹, G Noonan¹, M Uosis-Martin¹, D Lyth¹, O Bardell-Cox¹, J Massam¹, P Schofield¹, A Lyons¹, D Clare¹, J Maclean¹, A Smith¹, V Savage¹, S Mohmed¹, C Charrier¹, A-M Salisbury¹, E Moyo¹, N Ooi¹, N Chalam-Judge¹, J Cheung¹, N R Stokes¹, S Best¹, M Craighead¹, R Armer¹, A Huxley¹

Affiliation

¹ Redx Anti-Infectives Ltd Alderley Park Macclesfield SK10 4TG Cheshire UK.

Abstract

Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC₉₀ of 0.5 μg mL^-1 against Staphylococcus aureus, favourable in vitro pharmacokinetic properties, selectivity versus human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.