azamulin and Gram-Positive-Bacterial-Infections

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.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Drug Design; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Molecular Structure; Pleuromutilins; Polycyclic Compounds; Solubility; Stereoisomerism; Water