Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

被引：99

作者：

Li, Xiaokai ^{[2
]}

Liu, Nina ^{[2
]}

Zhang, Huaning ^{[2
]}

Knudson, Susan E. ^{[1
]}

Slayden, Richard A. ^{[1
]}

Tonge, Peter J. ^{[2
]}

机构：

[1] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

[2] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Dept Chem, Stony Brook, NY 11794 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 21期

基金：

美国国家卫生研究院;

关键词：

Mycobacterium tuberculosis; MenB; Menaquinone; 1,4-Dihydroxy-2-naphthoyl-CoA synthase; 1,4-Benzoxazine; BIOSYNTHESIS; VITAMIN-K-2; PERSPECTIVE; DERIVATIVES; DISCOVERY; POTENT;

D O I：

10.1016/j.bmcl.2010.08.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. In order to identify leads that target MenB, the 1,4-dihydroxy-2-naphthoyl-CoA synthase from Mycobacterium tuberculosis, a high-throughput screen was performed. Several 1,4-benzoxazines were identified in this screen and subsequent SAR studies resulted in the discovery of compounds with excellent antibacterial activity against M. tuberculosis H37Rv with MIC values as low as 0.6 mu g/ml. The 1,4-benzoxazine scaffold is thus a promising foundation for the development of antitubercular agents. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6306 / 6309

页数：4

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