Abstract
In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate additional H-bonding functions and can be more water soluble than their naphthyridinone progenitors; diazepine 16c is shown to be efficacious in a mouse infection model.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Anti-Bacterial Agents / therapeutic use
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Azepines / chemistry*
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Azepines / pharmacology*
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Azepines / therapeutic use
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / metabolism*
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Escherichia coli Infections / drug therapy
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Mice
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Models, Molecular
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Protein Binding
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Staphylococcal Infections / drug therapy
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / enzymology
Substances
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Anti-Bacterial Agents
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Azepines
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)