Design, synthesis and structure-activity relationship evaluation of novel LpxC inhibitors as Gram-negative antibacterial agents. Issue 2 (15th January 2018)

• Record Type: Journal Article
• Authors: Ding, Shi; Dai, Rui-Yang; Wang, Wen-Ke; Cao, Qiao; Lan, Le-Fu; Zhou, Xian-Li; Yang, Yu-She
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 2(2018)
• Page Start: 94
• Page End: 102
• Publication Date: 2018-01-15
• Subjects: Gram-negative bacteria infection -- LpxC inhibitor -- Structure-activity relationship -- Zinc binding group -- Liver microsomal stability; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.005
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 ofYDL-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.