Abstract
Although earlier pleuromutilin analogues showed potent in vitro antibacterial activity against some Gram-positive pathogens, their in vivo efficacy was low because of insufficient pharmacokinetic properties. We designed novel thioether pleuromutilin derivatives having a purine ring as a polar and water solubilizing group and identified a promising pleuromutilin analogue 6 with good solubility in water ( approximately 50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Disease Models, Animal
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Diterpenes / chemical synthesis
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Diterpenes / chemistry
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Diterpenes / pharmacology
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Dose-Response Relationship, Drug
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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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Gram-Positive Bacterial Infections / drug therapy
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Mice
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Microbial Sensitivity Tests
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Molecular Structure
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Pleuromutilins
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Polycyclic Compounds
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Solubility
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Stereoisomerism
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Water / chemistry
Substances
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Anti-Bacterial Agents
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Diterpenes
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Polycyclic Compounds
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Water