Synthesis and antibacterial evaluation of a novel series of rifabutin-like spirorifamycins
- 作者：In Ho Kim ; Keith D. Combrink ; Zhenkun Ma ; Katrina Chapo ; Dalai Yan ; Paul Renick ; Timothy W. Morris ; Mark Pulse ; Jerry W. Simecka ; Charles Z. Ding
- 关键词：Rifamycin ; Rifabutin ; Spirorifamycin ; RNA polyerase inhibitors ; Synthesis ; Rifampin-resistant ; Ansamycin ; Staphylococcus aureus ; Antibacterial
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 March 2007
- 卷：17
- 期：5
- 页码：1181-1184
- 文件大小：140 K
摘要
A novel series of spirorifamycins was synthesized and their antibacterial activity evaluated both in vitro and in vivo. This new series of rifamycins shows excellent activity against Staphylococcus aureus that is equivalent to rifabutin. However, some compounds of the series exhibit lower MICs than rifabutin against rifampin-resistant strains of S. aureus. Further, compound 2e exhibits comparable efficacy in vivo in a murine model of S. aureus septicemia model following administration by either oral or parenteral dosing routes.