Discovery and initial development of a novel class of antibacterials:: Inhibitors of Staphylococcus aureus transcription/translation
Discovery and initial development of a novel class of antibacterials:: Inhibitors of Staphylococcus aureus transcription/translation
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DOI：
10.1016/j.bmcl.2006.09.044
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发表时间：
2006-12-15
影响因子：
2.7
通讯作者：
Marotti, Keith R.
中科院分区：
文献类型：
--
作者：
Larsen, Scott D.;Hester, Matthew R.;Marotti, Keith R.
新型细菌转录/翻译（TT）抑制剂1是通过高通量筛选和探索性药物化学相结合的方法鉴定的。邻氨基苯甲酸部分和磺酰胺胺多样性的初始优化是通过1-和二维溶液相库完成的，导致铅的MIC从64 μ g/mL提高到8 μ g/mL（化合物4 I）。随后的中心芳环的改性和磺酰胺胺的进一步精制需要在Wang树脂上开发固相路线。由此产生的库产生了许多强效抗菌药物，其MIC为
The novel bacterial transcription/translation (TT) inhibitor 1 was identified through a combination of high throughput screening and exploratory medicinal chemistry. Initial optimization of the anthranilic acid moiety and sulfonamide amine diversity was accomplished via 1- and two-dimensional solution phase libraries, resulting in an improvement in the MIC of the lead from 64 to 8 mu g/mL (compound 4I). Subsequent modification of the central aromatic ring and further refinement of the sulfonamide amines required the development of a solid phase route on Wang resin. The resulting libraries generated a number of potent antibacterials with MICs of