ATP‐competitive inhibitors of DNA gyrase and topoisomerase IV are among the most interesting classes of antibacterial drugs that are unrepresented in the antibacterial pipeline. We developed 32 new N‐phenylpyrrolamides and evaluated them against DNA gyrase and topoisomerase IV from E. coli and Staphylococcus aureus. Antibacterial activities were studied against Gram‐positive and Gram‐negative bacterial strains. The most potent compound displayed an IC₅₀ of 47 nm against E. coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5 μm against the Gram‐positive Enterococcus faecalis. Some compounds displayed good antibacterial activities against an efflux‐pump‐deficient E. coli strain (MIC=6.25 μm) and against wild‐type E. coli in the presence of efflux pump inhibitor PAβN (MIC=3.13 μm). Here we describe new findings regarding the structure–activity relationships of N‐phenylpyrrolamide DNA gyrase B inhibitors and investigate the factors that are important for the antibacterial activity of this class of compounds.

中文翻译：

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合成和评估N-苯基吡咯酰胺作为DNA促旋酶B抑制剂

DNA促旋酶和拓扑异构酶IV的ATP竞争性抑制剂是在抗菌产品中没有代表的最有趣的一类抗菌药物。我们开发了32种新的N-苯基吡咯酰胺，并针对来自大肠杆菌和金黄色葡萄球菌的DNA促旋酶和拓扑异构酶IV进行了评估。研究了对革兰氏阳性和革兰氏阴性细菌菌株的抗菌活性。最有效的化合物显示的IC ₅₀的子47n米针对大肠杆菌DNA促旋酶，和12.5μ的最小抑制浓度（MIC）米对抗革兰氏阳性粪肠球菌。一些化合物显示针对外排泵缺陷良好的抗菌活性的大肠杆菌菌株（MIC = 6.25μ米）和对野生型大肠杆菌在外排泵的存在抑制剂PAβN（MIC = 3.13μ米）。在这里，我们描述了有关N-苯基吡咯酰胺DNA旋转酶B抑制剂的结构-活性关系的新发现，并研究了对于此类化合物的抗菌活性重要的因素。