Synthesis and structure-activity relationship of novel inhibitors of the prokaryotic divisome protein FtsZ

Antimicrobial resistance is an ever growing cause for concern among health authorities across the world. In fact, therapeutic options for life- threatening infections are rapidly being ruled out and there is a strong urge to discover and develop potent drugs with innovative mechanisms of action. In the search for new targets, FtsZ (Filamentous temperature sensitive Z) was identified as a very promising candidate. Functionally a GTP-ase, it plays a crucial role in the bacterial cell division process and is widely and specifically expressed among Prokaryotes. In recent years, our research group developed and synthesized a class of FtsZ inhibitors with interesting antimicrobial activity against drug-resistant strains and further expanded on their SAR through a series of isosteric, positional or substituent modifications on the heterocyclic scaffold. The aim of the present communication is to summarize the synthetic pathways and the SAR studies for this class of compounds, characterized by differently substituted heterocycles linked by a methylenoxy-bridge to a 2,6-difluorobenzamide.