Huang Ju, Liu Hongtao, Liu Mingliang, Zhang Rui, Li Linhu, Wang Bin, Wang Minghua, Wang Chunlan, Lu Yu
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Department of Pharmacy, Hebei General Hospital, Hebei, Shijiazhuang 050051, China.
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5058-63. doi: 10.1016/j.bmcl.2015.10.027. Epub 2015 Oct 22.
A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs: <0.25 μg/mL) and MDR-MTB 6133 (MICs: 0.03-0.054 μg/mL). The target compounds 21-24 are generally poor against the Gram-negative strains, but 21a-j and 22a-c have potent potency (MICs: <0.008-32 μg/mL) against all of the tested Gram-positive strains including MRSA and MRSE with a few exceptions, and the most active compounds 21d, 21e and 22a-c (MICs: <0.008-32 μg/mL) were found to be comparable to or better than moxifloxacin, and 2->250 times more potent than ciprofloxacin and levofloxacin.
设计、合成了一系列含有肟官能化吡咯烷部分的新型1-[(1R,2S)-2-氟环丙基]萘啶酮衍生物21-24，并对其生物活性进行了评估。我们的结果表明，化合物21a、21e和21j对结核分枝杆菌H37Rv ATCC 27294（MIC：<0.25μg/mL）和耐多药结核分枝杆菌6133（MIC：0.03-0.054μg/mL）表现出相当的活性。目标化合物21-24对革兰氏阴性菌一般表现不佳，但21a-j和22a-c对包括耐甲氧西林金黄色葡萄球菌和耐甲氧西林表皮葡萄球菌在内的所有测试革兰氏阳性菌具有强效活性（MIC：<0.008-32μg/mL），少数例外情况除外，最具活性的化合物21d、21e和22a-c（MIC：<0.008-32μg/mL）被发现与莫西沙星相当或优于莫西沙星，且比环丙沙星和左氧氟沙星强2至250倍以上。
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