The ATP binding site located on the subunit B of DNA gyrase is an attractive target for the development of new antibacterial agents. In recent decades, several small-molecule inhibitor classes have been discovered but none has so far reached the market. We present here the discovery of a promising new series of N-phenylpyrrolamides with low nanomolar IC₅₀ values against DNA gyrase, and submicromolar IC₅₀ values against topoisomerase IV from Escherichia coli and Staphylococcus aureus. The most potent compound in the series has an IC₅₀ value of 13 nM against E. coli gyrase. Minimum inhibitory concentrations (MICs) against Gram-positive bacteria are in the low micromolar range. The oxadiazolone derivative 11a, with an IC₅₀ value of 85 nM against E. coli DNA gyrase displays the most potent antibacterial activity, with MIC values of 1.56 μM against Enterococcus faecalis, and 3.13 μM against wild type S. aureus, methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The activity against wild type E. coli in the presence of efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PAβN) is 4.6 μM.

位于 DNA 促旋酶 B 亚基上的 ATP 结合位点是开发新抗菌剂的一个有吸引力的目标。近几十年来，已经发现了几种小分子抑制剂类别，但迄今为止还没有一种进入市场。我们在此展示了对来自大肠杆菌和金黄色葡萄球菌的拓扑异构酶 IV具有低纳摩尔 IC ₅₀值和亚微摩尔 IC _{50值的有前景的新系列}N-苯基吡咯酰胺的发现。该系列中最有效的化合物对大肠杆菌的 IC ₅₀值为 13 nM回旋。对革兰氏阳性菌的最低抑菌浓度 (MIC) 在低微摩尔范围内。恶二唑酮衍生物11a对大肠杆菌DNA 促旋酶的 IC ₅₀值为 85 nM，显示出最有效的抗菌活性，对粪肠球菌的 MIC 值为 1.56 μM ，对野生型金黄色葡萄球菌、耐甲氧西林S.的 MIC 值为 3.13 μM . 金黄色葡萄球菌(MRSA) 和耐万古霉素肠球菌(VRE)。在外排泵抑制剂苯丙氨酸-精氨酸 β-萘酰胺 (PAβN) 存在下，对野生型大肠杆菌的活性为 4.6 μM。