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.