The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones.

Abstract

The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 microg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of alpha-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.

• Authors: Fred L Ciske, Michael R Barbachyn, Michael J Genin, Kevin C Grega, Chi Sing Lee, Lester A Dolak, Eric P Seest, William Watt, Wade J Adams, Janice M Friis, Charles W Ford, Gary E Zurenko
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 13 Issue 23 Pg. 4235-9 (Dec 01 2003) ISSN: 0960-894X [Print] England
• PMID: 14623008 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Hydroquinones
• Indoles
• Oxazines
• Oxazolidinones

Topics

• Anti-Bacterial Agents (chemical synthesis, pharmacokinetics, pharmacology)
• Drug Design
• Drug Resistance, Bacterial
• Gram-Negative Bacteria (drug effects)
• Gram-Positive Bacteria (drug effects)
• Hydroquinones (chemical synthesis, pharmacokinetics, pharmacology)
• Indoles (chemical synthesis, pharmacokinetics, pharmacology)
• Microbial Sensitivity Tests
• Oxazines (chemical synthesis, pharmacokinetics, pharmacology)
• Oxazolidinones (chemical synthesis, pharmacokinetics, pharmacology)
• Structure-Activity Relationship