Design, synthesis and structure-activity relationship evaluation of novel LpxC inhibitors as Gram-negative antibacterial agents

[Display omitted] LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To develop novel LpxC inhibitors with good antibacterial activities and biological metabolism, we summarized the basic skeleton of reported LpxC i...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2018-01, Vol.28 (2), p.94-102
Main Authors: Ding, Shi, Dai, Rui-Yang, Wang, Wen-Ke, Cao, Qiao, Lan, Le-Fu, Zhou, Xian-Li, Yang, Yu-She
Format: Article
Language:English
Subjects:
Gram-negative bacteria infection
Liver microsomal stability
LpxC inhibitor
Structure-activity relationship
Zinc binding group
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Summary:[Display omitted] LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To develop novel LpxC inhibitors with good antibacterial activities and biological metabolism, we summarized the basic skeleton of reported LpxC inhibitors, designed and synthesized several series of compounds and tested their antibacterial activities against Escherichial coli and Pseudomonas aeruginosa in vitro. Structure-activity relationships have been discussed in this article. The metabolism stability of YDL-2, YDL-5, YDL-8, YDL-14, YDL-20–YDL-23 have been evaluated in liver microsomes, which indicated that the 2-amino isopropyl group may be a preferred structure than the 2-hydroxy ethyl group in the design of LpxC inhibitors.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.12.005