New Arene and/or Heteroarene‐Linked 1,3,4‐Oxadiazoles: Synthesis of Potential Methicillin‐Resistant <i>Staphylococcus aureus</i> and Vancomycin‐Resistant <i>Enterococcus</i> Inhibitors

Abstract Bacterial infections, particularly those associated with methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcus (VRE), threaten public health and economies, with rising antibiotic resistance resulting in more deaths yearly. In this study, we investigated the bacterial inhibitory activity of some new 1,3,4‐oxadiazoles prepared, in good yields, using a two‐step tandem protocol. Therefore, the appropriate N ‐benzoylhydrazones were prepared first, then, without isolation, underwent oxidative‐cyclization in the presence of chloramine trihydrate. More 4‐acyloxyphenyl‐linked 1,3,4‐oxadiazoles were prepared by the pyridine‐mediated acylation of 2‐(4‐hydroxyphenyl)‐1,3,4‐oxadiazoles with the appropriate acyl chlorides. Some new products demonstrated good activity, particularly against S. aureus and Enterococcus faecalis strains. The 4‐(5‐(furan‐2‐yl)‐1,3,4‐oxadiazol‐2‐yl)phenyl acetate showed comparable antibacterial activity to ciprofloxacin, with MIC/MBC values up to 3.6/7.2 µM against the previous strains. Moreover, it demonstrated good inhibitory activity against different MRSA and VRE strains when compared to linezolid. It had MIC/MBC values of 7.2/14.4 and 14.4/57.8 µM against MRSA and VRE strains, respectively.