Water-soluble pleuromutilin derivative with excellent in vitro and in vivo antibacterial activity against Gram-positive pathogens
Water-soluble pleuromutilin derivative with excellent in vitro and in vivo antibacterial activity against Gram-positive pathogens
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DOI：
10.1021/jm8000136
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发表时间：
2008-04-10
影响因子：
7.3
通讯作者：
Kato, Shiro
中科院分区：
文献类型：
--
作者：
Hirokawa, Yoshimi;Kinoshita, Hironori;Kato, Shiro
虽然早期截短侧耳素类似物对一些革兰氏阳性病原体显示出有效的体外抗菌活性，但由于药代动力学性质不足，其体内功效较低。我们设计了具有嘌呤环作为极性和水增溶性基团的新型硫醚截短侧耳素衍生物，并鉴定了具有良好水溶性（类似于50 mg/mL）的有前途的截短侧耳素类似物6。化合物6对一些革兰氏阳性菌株，包括耐药病原体，表现出优异的体外和体内抗菌活性。
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 (similar to 50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.