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.
R Kirk  1 ,  A Ratcliffe  1 ,  G Noonan  1 ,  M Uosis-Martin  1 ,  D Lyth  1 ,  O Bardell-Cox  1 ,  J Massam  1 ,  P Schofield  1 ,  A Lyons  1 ,  D Clare  1 ,  J Maclean  1 ,  A Smith  1 ,  V Savage  1 ,  S Mohmed  1 ,  C Charrier  1 ,  A-M Salisbury  1 ,  E Moyo  1 ,  N Ooi  1 ,  N Chalam-Judge  1 ,  J Cheung  1 ,  N R Stokes  1 ,  S Best  1 ,  M Craighead  1 ,  R Armer  1 ,  A Huxley  1
Affiliations
  • 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.

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