Water-Soluble Pleuromutilin Derivative with Excellent in Vitro and in Vivo Antibacterial Activity against Gram-Positive Pathogens

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• 作者：Yoshimi Hirokawa ; Hironori Kinoshita ; Tomoyuki Tanaka ; Katsuhisa Nakata ; Noriyuki Kitadai ; Koichi Fujimoto ; Shigeki Kashimoto ; Tsuyoshi Kojima ; Shiro Kato
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：April 10, 2008
• 年：2008
• 卷：51
• 期：7
• 页码：1991 - 1994
• 全文大小：85K
• 年卷期：v.51,no.7(April 10, 2008)
• ISSN：1520-4804

文摘

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 (~50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.