Recent Developments in Oxazolidinones as Potent Antibacterials

摘要

Many common gram-positive pathogens such as Staphylococcus aureus, Enterococcus species, and Streptococcus pneumoniae have become increasingly resistant to antibacterial agents. Con- sequently potent new drugs with activity against gram positive bacteria are immediately needed. Oxazolidinones which represent a promising new class of potent antibacterial agent have a unique mechanism of inhibiting bacterial protein synthesis. The commercial success of linezolid, the only FDA approved oxazolidinone have significant efforts to developed new antibacterial agents in the oxazolidinone class. Linezolid shows promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram positive pathogens such as methicillin resistant Staphylococcus aureus, vancomycin resistant enterococci, and penicillin resistant Streptococcus pneumoniae. New agents with greater potency and new spectra of activity could arise from further modification of the oxazolidinone rings. Three oxazolidinones are currently undergoing clinical trials. Cubist Pharmaceuticals has announced that its new drug application (NDA) for tedizolid phosphate(TR-701) has been accepted by the US FDA for priority review. TR-701 used for the treatment of acute bacterial skin and skin structure infections (ABSSSI). TR-701 is a once daily oxazolidinone being developed for both intravenous and oral administration for the treatment of serious Gram positive infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Rib-X Pharmaceuticals Reports Positive Phase 2 Study Results for Radezolid in Community Acquired Pneumonia. Sutezolid (PNU-100480,PF-02341272) has shown promising efficacy in a phase Ila study in patients suffering from TB in South Africa. AstraZeneca finish phase 2a clinical trials in December 2013 and work ongoing to position AZD5847 for phase 2b by mid 2014 for the treatment of tuberculosis. This review makes an attempt to summarize the work carried out in the period from2000 until 2013.