Discovery of Novel and Ligand-Efficient Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferase

被引：56
|
作者：
Rackham, Mark D. [1 ]
Brannigan, James A. [2 ]
Moss, David K. [3 ]
Yu, Zhiyong [1 ]
Wilkinson, Anthony J. [2 ]
Holder, Anthony A. [3 ]
Tate, Edward W. [1 ]
Leatherbarrow, Robin J. [1 ]
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England
[2] Univ York, Dept Chem, York Struct Biol Lab, York YO10 5DD, N Yorkshire, England
[3] MRC Natl Inst Med Res, Div Parasitol, London NW7 1AA, England
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 01期
基金：
英国医学研究理事会; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词：
DESIGN;
D O I：
10.1021/jm301474t
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (PO and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic activity in vitro. The binding mode of this series was determined by crystallography and shows a novel binding mode for the benzothiophene ring.
引用
收藏
页码：371 / 375
页数：5
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