Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase

…, SP Canavan, PR Hirst, C Ramsey, AMW Stead…

Index: Boa, Andrew N.; Canavan, Shane P.; Hirst, Paul R.; Ramsey, Christopher; Stead, Andrew M.W.; McConkey, Glenn A. Bioorganic and Medicinal Chemistry, 2005 , vol. 13, # 6 p. 1945 - 1967

Full Text: HTML

Citation Number: 60

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 (IC50 880μM) whereas several members of the series inhibited PfDHODH. Unexpectedly, replacement of the carboxylic acid required for ...

 Related Synthetic Route

~%

~%

~92%

~58%

~80%

~83%

~%

~%

~%

~%

~94%

~%

~%

~%

~66%

~10%

~%

~%

~78%

~%

~%

~%

~%