Oxazolidinone antimicrobials: a patent review (2012-2015)

ABSTRACT

Introduction: Antimicrobial resistance in Gram-positive bacteria is a major health care issue. This review summarizes patent publications from 2012 to 2015 that divulged novel oxazolidinones as antibacterial agents.

Areas covered: A total of 25 patents obtained from Espacenet, WIPO Patentscope and FreePatentsOnline, and AcclaimIP search engines were reviewed. The patents were scrutinized based on the novelty of the compounds, their antibacterial activity (MIC, µg/mL), and the process of preparation. The oxazolidinones with promising antibacterial activity were classified according to the following structural diversities, as biaryl heterocyclic, fused heteroaryl rings containing oxazolidinones, and others. The biaryl heterocyclic, fused heteroaryl, benzoxazine, and the 1H-pyrazol-1-yl containing oxazolidinone derivatives demonstrated potent antibacterial activities superior to linezolid against Gram-positive bacteria. Some derivatives were effective against standard strains of Gram-negative bacteria, namely Moraxella catarrhalis ATCC A894, and Escherichia coli ATCC 25922. In addition, a patent disclosed a structural isomer of linezolid with marginal activity against the aerobic Gram-negative bacteria MDR Stenotrophomonas (Xanthomonas) maltophilia, while linezolid and vancomycin did not inhibit growth. Finally, some derivatives showed activity against respiratory infectious diseases’ causative agents, such as B. anthracis, B. mallei, Y. pestis, and M. pneumoniae.

Expert opinion: Overall, there is limited in vivo data to support the potential clinical advancement of the currently reported novel derivatives.

KEYWORDS:

• Antibacterial agents
• antimicrobials
• bacterial-resistance
• fluoroquinolone-oxazolidinone hybrids
• Gram-negative bacteria
• Gram-positive bacteria
• linezolid
• oxazolidinone
• tedizolid

Article highlights

• Twenty five patents publications from 2012 to 2015 were selected for review.

• The patents were obtained from free patent search engines such as Espacenet and WIPO patentscope.

• Heteroaryl containing oxazolidinones showed potent in vitro antibacterial activities superior to linezolid against Gram-positive bacteria.

• Some derivatives showed activity against selected Gram-negative bacteria strains, M. catarrhalis and E. coli.

• There was limited in vivo antimicrobial data to affirm potential clinical effectiveness of the compounds.

• No in vivo data are presented to confirm the safety profiles of reported oxazolidinone derivatives.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank the Faculty of Pharmacy, Kuwait University for providing the facilities during the preparation of this manuscript.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.