The oxazolidinones: past, present, and future.

Abstract

The success of linezolid stimulated significant efforts to discover new agents in the oxazolidinone class. Over a dozen oxazolidinones have reached the clinic, but many were discontinued due to lack of differentiated potency, inadequate pharmacokinetics, and safety risks that included myelosuppression. Four oxazolidinones are currently undergoing clinical evaluation. The Trius Therapeutics compound tedizolid phosphate (formerly known as torezolid phosphate, TR-701, DA-7218), the most advanced, is in phase 3 clinical trials for acute bacterial skin and skin structure infections. Rib-X completed two phase 2 studies for radezolid (Rx-01_667, RX-1741) in uncomplicated skin and skin structure infections and community-acquired pneumonia. Pfizer and AstraZeneca have each identified antitubercular compounds that have completed phase 1 studies: sutezolid (PNU-100480, PF-02341272) and AZD5847 (AZD2563), respectively. The oxazolidinones share a relatively low frequency of resistance largely due to the requirement of mutations in 23S ribosomal RNA genes. However, maintaining potency against strains carrying the mobile cfr gene poses a challenge for the oxazolidinone class, as well as other 50S ribosome inhibitors that target the peptidyl transferase center.

• Authors: Karen Joy Shaw, Michael R Barbachyn
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1241 Pg. 48-70 (Dec 2011) ISSN: 1749-6632 [Electronic] United States
• PMID: 22191526 (Publication Type: Historical Article, Journal Article, Review)
• Copyright: © 2011 New York Academy of Sciences.

Chemical References

• Anti-Bacterial Agents
• Oxazolidinones

Topics

• Anti-Bacterial Agents (chemistry, history, pharmacology)
• Bacterial Infections (drug therapy)
• Clinical Trials as Topic
• Drug Resistance, Bacterial (genetics)
• Genes, Bacterial
• History, 20th Century
• History, 21st Century
• Humans
• Mutation
• Oxazolidinones (chemistry, history, pharmacology)