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  • Title: Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase.
    Author: Boa AN, Canavan SP, Hirst PR, Ramsey C, Stead AM, McConkey GA.
    Journal: Bioorg Med Chem; 2005 Mar 15; 13(6):1945-67. PubMed ID: 15727850.
    Abstract:
    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 (IC(50) 880 microM) 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.
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