设计、合成及 C(4)取代单环β-内酰胺类化合物作为抗多重耐药革兰氏阴性菌的抗菌药物的生物学评价。
Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria.
机构信息
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Department of Microbiology, Sichuan Primed Shines Bio-tech Co., Ltd, Chengdu, Sichuan Province, 610041, China.
出版信息
Eur J Med Chem. 2018 May 10;151:98-109. doi: 10.1016/j.ejmech.2018.03.058. Epub 2018 Mar 23.
A series of novel pyridone conjugated monobactams with various substituents at the (4) position were synthesized and evaluated for their antibacterial activities against a panel of multidrug-resistant (MDR) Gram-negative bacteria in vitro. Compounds 46d, 54 and 75e displayed good to moderate activities against P. aeruginosa, among which the activity of 75e against P. aeruginosa was comparable to that of BAL30072 under iron limitation condition. Compounds 35, 46d, 54, 56a, 56c and 56d exhibited good to excellent antibacterial activities against E. coli and K. pneumoniae, which were comparable or superior to that of BAL30072. In vitro liver microsomal stability was further evaluated and the results manifested that Compounds 35, 46d and 54 were metabolically stable in human liver microsomes.
一系列新型吡啶酮共轭单环 β-内酰胺类化合物被合成出来，并在体外对一系列耐多药（MDR）革兰氏阴性菌进行了抗菌活性评估。化合物 46d、54 和 75e 对铜绿假单胞菌表现出良好至中等的活性，其中 75e 对铜绿假单胞菌的活性在缺铁条件下与 BAL30072 相当。化合物 35、46d、54、56a、56c 和 56d 对大肠杆菌和肺炎克雷伯菌表现出良好至优异的抗菌活性，与 BAL30072 相当或更优。进一步评估了体外肝微粒体稳定性，结果表明化合物 35、46d 和 54 在人肝微粒体中代谢稳定。
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