Design, synthesis, and structure-activity relationships of pyrazole derivatives as potential FabH inhibitors

被引：87

作者：

Lv, Peng-Cheng ^{[1
]}

Sun, Juan ^{[1
]}

Luo, Yin ^{[1
]}

Yang, Ying ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

基金：

中国国家自然科学基金; 美国国家科学基金会;

关键词：

Design; Synthesis; FabH inhibitors; Antibacterial; Pyrazole derivatives; Structure-activity relationship; ACYL-CARRIER-PROTEIN; SYNTHASE-III; ANTITUMOR-ACTIVITY; ANTIBACTERIAL ACTIVITY; ANTIMICROBIAL AGENTS; CONDENSING ENZYME; ESCHERICHIA-COLI; IDENTIFICATION; NUCLEOSIDES; ETHERS;

D O I：

10.1016/j.bmcl.2010.05.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and - \negative bacteria. Fifty-six 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-(4-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) ethanone (12) and 1-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl) ethanone (13) were potent inhibitors of E. coli FabH. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4657 / 4660

页数：4

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