Abstract
Novel pyranosyl analogues of SB-219383 have been synthesised to elucidate the structure-activity relationships around the pyran ring. Analogues with highly potent stereoselective and bacterioselective inhibition of bacterial tyrosyl tRNA synthetase have been identified. A major reduction in the overall polarity of the molecule can be tolerated without loss of the nanomolar level of inhibition.
MeSH terms
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / chemistry*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Furans / chemistry*
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Furans / pharmacology
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Molecular Conformation
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Molecular Structure
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Pyrans / chemistry*
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / metabolism
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Tyrosine-tRNA Ligase / antagonists & inhibitors*
Substances
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Bacterial Proteins
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Bridged Bicyclo Compounds, Heterocyclic
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Enzyme Inhibitors
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Furans
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Pyrans
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SB 219383
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Tyrosine-tRNA Ligase