Structure-based discovery of LpxC inhibitors

被引：18

作者：

Zhang, Jing ^{[1
]}

Chan, Audrey ^{[1
]}

Lippa, Blaise ^{[1
]}

Cross, Jason B. ^{[1
]}

Liu, Christopher ^{[1
]}

Yin, Ning ^{[1
]}

Romero, Jan Antoinette C. ^{[1
]}

Lawrence, Jonathan ^{[1
]}

Heney, Ryan ^{[1
]}

Herradura, Prudencio ^{[1
]}

Goss, Jennifer ^{[1
]}

Clark, Cynthia ^{[1
]}

Abel, Cassandra ^{[1
]}

Zhang, Yanzhi ^{[1
]}

Poutsiaka, Katherine M. ^{[1
]}

Epie, Felix ^{[1
]}

Conrad, Mary ^{[1
]}

Mahamoon, Azard ^{[1
]}

Kien Nguyen ^{[1
]}

Chavan, Ajit ^{[1
]}

Clark, Edward ^{[1
]}

Li, Tong-chuan ^{[1
]}

Cheng, Robert K. ^{[2
]}

Wood, Michael ^{[2
]}

Andersen, Ole A. ^{[2
]}

Brooks, Mark ^{[2
]}

Kwong, Jason ^{[2
]}

Barker, John ^{[2
]}

Parr, Ian Barrie ^{[1
]}

Gu, Yugui ^{[1
]}

Ryan, M. Dominic ^{[1
]}

Coleman, Scott ^{[1
]}

Metcalf, Chester A., III ^{[1
]}

机构：

[1] Cubist Pharmaceut Inc, 65 Hayden Ave, Lexington, MA 02421 USA

[2] Evotec UK Ltd, 114 Innovat Dr,Milton Pk, Abingdon OX14 4RZ, Oxon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 08期

关键词：

LpxC; Escherichia coli; Klebsiella pneumonia; Pseudomonas aeruginosa; Acinetobacter baumannii; Antibacterial; ZINC-DEPENDENT DEACETYLASE; CRYSTAL-STRUCTURE; MECHANISM; ESKAPE;

D O I：

10.1016/j.bmcl.2017.03.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria presents a serious threat for public health. Novel antimicrobials that could overcome the resistance problems are urgently needed. UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc-based deacetylase that catalyzes the first committed step in the biosynthesis of lipid A, which is essential for the survival of Gram-negative bacteria. Our efforts toward the discovery of novel LpxC inhibitors are presented herein. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：1670 / 1680

页数：11

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