Abstract
Dual inhibitors of bacterial gyrB and parE based on a 5-(2-pyrimidinyl)-imidazo[1,2-a]pyridine template exhibited MICs (microg/mL) of 0.06-64 (Sau), 0.25-64 (MRSA), 0.06-64 (Spy), 0.06-64 (Spn), and 0.03-64 (FQR Spn). Selected examples were efficacious in mouse sepsis and lung infection models at <50mg/kg (PO dosing).
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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DNA Gyrase / metabolism*
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DNA Topoisomerase IV / metabolism*
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Gram-Positive Bacteria / drug effects
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Imidazoles / therapeutic use
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Lung / drug effects
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Lung / microbiology
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Mice
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Microbial Sensitivity Tests
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Pyridines / chemistry
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Pyridines / pharmacology*
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Pyridines / therapeutic use*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use
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Rats
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Sepsis / drug therapy
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Imidazoles
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Pyridines
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Pyrimidines
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imidazole
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DNA Topoisomerase IV
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DNA Gyrase
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pyrimidine