金黄色葡萄球菌中诺氟沙星外排泵的2-芳基-1H-吲哚抑制剂的构效关系
Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA efflux pump in Staphylococcus aureus.
作者信息
Ambrus Joseph I, Kelso Michael J, Bremner John B, Ball Anthony R, Casadei Gabriele, Lewis Kim
机构信息
School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.
出版信息
Bioorg Med Chem Lett. 2008 Aug 1;18(15):4294-7. doi: 10.1016/j.bmcl.2008.06.093. Epub 2008 Jul 2.
Abstract
The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as NorA efflux pump inhibitors indicated 5-nitro-2-(3-methoxycarbonyl)phenyl-1H-indole was a slightly more potent inhibitor than the lead INF55. A promising new antibacterial lead compound against S. aureus (2-phenyl-1H-indol-5-yl)-methanol, was also found.
摘要
通过钯或铑介导的方法或选择性亲电取代反应，已经实现了22种2-芳基-1H-吲哚的合成，其中包括12种新化合物。所有这三种方法均基于简单吲哚前体的衍生化。对这些吲哚以及2-苯基-1H-吲哚作为金黄色葡萄球菌NorA外排泵抑制剂的构效关系研究表明，5-硝基-2-(3-甲氧基羰基)苯基-1H-吲哚是一种比先导化合物INF55稍强的抑制剂。还发现了一种有前景的新型抗金黄色葡萄球菌抗菌先导化合物(2-苯基-1H-吲哚-5-基)甲醇。
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