Synthetic Strategies towards Imidazopyridinones and 7‐Azaoxindoles and their Evaluation as Antibacterial Agents

Abstract

Imidazopyridinones and 7‐azaoxindoles are two classes of heterocyclic compounds with only limited previous use in organic and medicinal chemistry. Various synthetic methods and routes have been evaluated to identify safe and robust chemistry to advanced imidazopyridinone building blocks and inhibitor structures. Preparation of the 7‐azaoxindoles was challenged by instability of the core scaffold. Key to the successful isolation of the target structure was development of a mild Suzuki cross‐coupling in non‐aqueous media. The imidazopyridinones were potent inhibitors of the E. coli thymidylate monophosphate kinase, while the 7‐azaoxindole showed low activity. The compounds were inactive in cell‐based studies, indicating poor cell wall penetration.

Halogenated Pyrrolopyrimidines with Low MIC on Staphylococcus aureus and Synergistic Effects with an Antimicrobial Peptide

“…Our previous efforts at targeting TMPK using enzyme assays have, unfortunately, arrived at compounds that are inactive in culture experiments [ 12 , 39 ]. In this study, we have, therefore, altered our strategy and used minimal inhibitory concentration assays to identify and improve antibacterial agents.…”

Activation of multiple stress responses in Staphylococcus aureus substantially lowers the minimal inhibitory concentration when combining two novel antibiotic drug candidates

“…The compounds L-1 and L-2 were prepared as shown in Supplementary Experimental Scheme 1 and accompanying experimental procedure. The compounds L-3, L-4, and L-5 were prepared as previously described ( Bugge et al, 2016 ; Blindheim et al, 2021a , b ). Kinase inhibitors containing carboxyl groups (PurvB, L-1, L-2, L-3, L-4, and L-5) were coupled to EAH Sepharose 4B beads (GE Healthcare, USA) and inhibitors with amino groups (Bis-X) were coupled to NHS-activated Sepharose 4 fast flow beads (GE Healthcare) according to manufacturer’s protocol.…”