Aryl‐Fluorocyclopropane β ‐Lactams with Activity Against Mycobacteroides abscessus and Mycobacterium bovis BCG

Abstract: A novel series of aryl‐α‐fluorocyclopropyl 1 and α,β,β‐trifluorocyclopropyl 2 β‐lactams have been prepared and their activity explored across various Mycobacteria and also the ESKAPE panel of pathogens. The most active of these compounds 1 a displayed good activity against clinically challenging Mycobacteria such as M. bovis BCG (MIC 0.39 mg/mL)) and did not show any significant activity against the ESKAPE pathogens indicating selectivity for this otherwise challenging class of pathogen. Compound 1 a was however rapidly metabolised and toxic to a human model cell line (HepG2) limiting its clinical development at this stage. The compounds were designed to exploit a fluoride ion elimination mechanism concomitant with β‐lactam ring opening, as the basis of a mechanism induced trigger to generate a reactive intermediate (suicide inhibition). In model alkoxide reactions a representative from both classes 1 and 2 resulted in β‐lactam ring opening but only the more active mono‐fluoro cyclopropane series 1 triggered fluoride ion elimination after ring opening and this may form the basis of its activity.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Aryl‐Fluorocyclopropane β ‐Lactams with Activity Against Mycobacteroides abscessus and Mycobacterium bovis BCG ; day:09 ; month:11 ; year:2024 ; extent:9 ; European journal of organic chemistry ; (09.11.2024) (gesamt 9)

Contributors, Places and Time

• Creator: Spurling, Dominic E. ; Baker, Emily J. ; Kingsley‐Moore, George ; Ppadath, Rifahath Mon Neyya ; More, Nachiket D. ; Al‐Maharik, Nawaf ; Harrison, James ; Cox, Jonathan A. G. ; O'Hagan, David

Further information

• DOI: 10.1002/ejoc.202401050
• URN: urn:nbn:de:101:1-2411101327295.323841426794
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:29 AM CEST