Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase
Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase
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DOI：
10.1016/j.bmc.2005.01.017
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发表时间：
2005-03-15
影响因子：
3.5
通讯作者：
McConkey, GA
中科院分区：
文献类型：
--
作者：
Boa, AN;Canavan, SP;McConkey, GA
一系列与布喹那（人二氢乳清酸脱氢酶（DHODH）抑制剂）相关的2-苯基喹啉-4-羧酸衍生物已被制备并评估为疟原虫恶性疟原虫的DHODH抑制剂。 Brequinar 对 PfDHODH 基本上没有活性（IC50 880 μM），而该系列的几个成员则抑制 PfDHODH。出乎意料的是，在抑制 PfDHODH 的二异丙基酰胺中，取代布雷喹那抑制 hDHODH 所需的羧酸并不是必需的。 (c) 2005 Elsevier Ltd. 保留所有权利。
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.