Asymmetric synthesis and biological evaluation of 1,2,4-Oxadiazoles analogues of Linezolid

Abstract

Oxazolidinones are a class of antibacterial agents which displayed activity againist a variety of gram-positive pathogens and are highly potent against multidrug-resistant bacteria. Linezolid is the first oxazolidinone antibiotic approved for clinical use but linezolid resistance began to appear. 1,2,4 – Oxadiazoles are known bioactive heterocycles whose activity has been often associated to their bioisosterism with amide or ester functionalities [1]. As results of a research project on the molecular design of heterocycle – based antibacterials to contrast Multi-Drug Resistance (MDR) [2], we report the synthesis of 1,2,4 - Oxadiazole analogues of Linezolid. The synthesis has been achieved by substitution of the morpholine ( C-ring ) with the Oxadiazole ring [3,4]. The central oxazolidinone ring was obtained through the Manninen reaction. Synthesized compounds showed good activity against Linezolid-resistant bacteria.