M. Drysdale, S. Hind, M. Jansen
Jan 13, 2000
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0
Influential Citations
23
Citations
Quality indicators
Journal
Journal of medicinal chemistry
Abstract
The synthesis and structure-activity relationship of a series of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids and esters and 2-amino-4-aryl-4-oxobut-2-enoic acids and esters as potent inhibitors of kynurenine-3-hydroxylase are described. These compounds are the most potent inhibitors of the kynurenine-3-hydroxylase enzyme so far disclosed. Additionally methyl 4-(3-chlorophenyl)-2-hydroxy-4-oxobut-2-enoate (2d), 4-(3-chlorophenyl)-2-hydroxy-4-oxobut-2-enoic acid (3d), methyl 4-(3-fluorophenyl)-2-hydroxy-4-oxobut-2-enoate (2f), and 4-(3-fluorophenyl)-2-hydroxy-4-oxobut-2-enoic acid (3f) prevent the increase in the interferon-gamma-induced synthesis of quinolinic acid in primary cultures of cultured human peripheral blood monocyte-derived macrophages.