Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria
Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria
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C(4)取代的单菌酰胺作为多重耐药革兰氏阴性菌抗菌剂的设计、合成和生物学评价
DOI：
10.1016/j.ejmech.2018.03.058
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发表时间：
2018-05-10
影响因子：
6.7
通讯作者：
Yang, Yushe
中科院分区：
文献类型：
--
作者：
Kou, Qunhuan;Wang, Ting;Yang, Yushe
合成了一系列4位取代的吡啶酮类单环内酰胺类化合物，并对其体外抗多药耐药革兰氏阴性菌活性进行了评价。化合物46 d、54和75 e对铜绿假单胞菌表现出良好至中等的活性，其中75 e在铁限制条件下对铜绿假单胞菌的活性与BAL30072相当。化合物35、46 d、54、56 a、56 c和56 d对大肠杆菌表现出良好的抑菌活性。埃希菌和pneumoniae，其与BAL30072相当或上级。进一步评价了化合物35、46 d和54的体外肝微粒体稳定性，结果表明化合物35、46 d和54在人肝微粒体中代谢稳定。(C)2018 Elsevier Masson SAS。All rights reserved.
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. (C) 2018 Elsevier Masson SAS. All rights reserved.