Scaffold hopping in the oxadiazole antibiotic structure leads to more active compounds

Abstract

Isosteric replacement of the oxadiazole ring by amide bond in the structure of new non-β-lactam antibiotics led to compounds with higher activity against Gram-positive pathogens of ESKAPE panel. A series of 17 compounds were synthesized by acylation of 4-(4-fluorophenoxy)aniline with various amino acids. The spirocyclic derivative with 6-methylsulfonyl-2,6-diazaspiro[3.4]octane moiety showed excellent minimum inhibitory concentrations of 0.093–0.75 μg ml−1 against a number of methicillin-resistant Staphylococcus aureus strains.