Regioselective synthesis of 4-chloro-3-hydroxyanthranilic acid, a potent in vitro inhibitor of 3-hydroxyanthranilic acid oxygenase activity from rat brain

Article abstract of DOI:10.1016/0223-5234(90)90210-T

In the kynurenine metabolic pathways of tryptophan in kidney, liver and brain, 3-hydroxyanthranilic oxygenase (3-HAO, EC 1.13.11.6) catalyses the conversion of 3-hydroxyanthranilic acid to quinolinic acid, an excitatory amino acid putatively involved in brain neurodegenerative disorders. The compound 4-chloro-3-hydroxyanthranilic acid is an irreversible inhibitor of 3-HAO in the liver and the kidney. We describe here a new, unambiguous regioselective synthesis of this inhibitor and verify its activity on 3-HAO at the brain level.