Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase

被引：70

作者：

Boa, AN

Canavan, SP

Hirst, PR

Ramsey, C

Stead, AMW

McConkey, GA

机构：

[1] Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Hull, Dept Chem, Kingston Upon Hull HU6 7RX, N Humberside, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 06期

关键词：

D O I：

10.1016/j.bmc.2005.01.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 2-phenyl quinoline-4-carboxylic acid derivatives related to brequinar, an inhibitor of human dihydroorotate dehydrogenase (DHODH), has been prepared and evaluated as inhibitors of DHODH from the malaria parasite Plasmodium falciparum. Brequinar was essentially inactive against PfDHODH (IC50 880 mu M) whereas several members of the series inhibited PfDHODH. Unexpectedly, replacement of the carboxylic acid required for brequinar to inhibit hDHODH was not essential in the diisopropylamides that inhibited PfDHODH. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1945 / 1967

页数：23

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