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.
MeSH terms
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Anti-Bacterial Agents* / chemical synthesis
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Anti-Bacterial Agents* / pharmacokinetics
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Anti-Bacterial Agents* / pharmacology
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Drug Design*
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Drug Resistance, Bacterial
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Gram-Negative Bacteria / drug effects
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Gram-Positive Bacteria / drug effects
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Hydroquinones* / chemical synthesis
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Hydroquinones* / pharmacokinetics
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Hydroquinones* / pharmacology
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Indoles* / chemical synthesis
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Indoles* / pharmacokinetics
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Indoles* / pharmacology
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Microbial Sensitivity Tests
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Oxazines* / chemical synthesis
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Oxazines* / pharmacokinetics
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Oxazines* / pharmacology
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Oxazolidinones* / chemical synthesis
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Oxazolidinones* / pharmacokinetics
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Oxazolidinones* / pharmacology
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Hydroquinones
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Indoles
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Oxazines
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Oxazolidinones