Oxazolidinones as versatile scaffolds in medicinal chemistry

Abstract

Oxazolidinone is a five-member heterocyclic ring with several biological applications in medicinal chemistry. Among the three possible isomers, 2-oxazolidinone is the most investigated in drug discovery. Linezolid was pioneered as the first approved drug containing an oxazolidinone ring as the pharmacophore group. Numerous analogues have been developed since its arrival on the market in 2000. Some have succeeded in reaching the advanced stages of clinical studies. However, most oxazolidinone derivatives reported in recent decades have not reached the initial stages of drug development, despite their promising pharmacological applications in a variety of therapeutic areas, including antibacterial, antituberculosis, anticancer, anti-inflammatory, neurologic, and metabolic diseases, among other areas. Therefore, this review article aims to compile the efforts of medicinal chemists who have explored this scaffold over the past decades and highlight the potential of the class for medicinal chemistry.

Fig. 1. A) Oxazolidinone isomers; B) first reported bioactive oxazolidinone derivatives reported; C) drugs containing the oxazolidinone scaffold.

Fig. 2. Oxazolidinones as antibacterial agents.

Fig. 3. Tricyclic oxazolidinone derivatives with activity against Gram-positive bacteria.

Fig. 4. Linezolid derivatives with modification in the C-ring.

Fig. 5. Oxazolidinone derivatives with antibacterial activity.

Fig. 6. Oxazolidinone as Gram-positive bacteria inhibitors.

Fig. 7. Gram-positive bacteria inhibitors.

Fig. 8. Antibacterial agents containing the oxazolidinone scaffold as the pharmacophore.

Fig. 9. Oxazolidinone with activity against Gram-negative bacteria.

Fig. 10. The trojan horse approach: siderophore–cephalosporin–eperezolid conjugate.

Fig. 11. Oxazolidinones as Gram-negative bacteria inhibitors.

Fig. 12. Oxazolidinone analogues active against ESKAPE bacteria.

Fig. 13. Tricyclic oxazolidinones as antituberculosis agents.

Fig. 14. Oxazolidinone as anticancer agents.

Fig. 15. Anticancer oxazolidinones.

Fig. 16. Oxazolidinones with anticancer activity acting against different targets.

Fig. 17. Oxazolidinones with antiviral activity.

Fig. 18. Oxazolidinones with anti-inflammatory activity.

Fig. 19. Oxazolidinones discovered for neurological disorders.

Fig. 20. Oxazolidinones developed for the treatment of metabolic syndromes.

Fig. 21. Oxazolidinones targeting FXa and T-box riboswitch RNA.

Fig. 22. Oxazolidinone derivatives with various activities.