2-Amino-4-{3'-hydroxyphenyl]-4-hydroxybutanoic Acid; A Potent Inhibitor of Rat and Recombinant Human Kynureninase

A novel structural analogue of kynurenine, 2-amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid 6, was synthesised as an inhibitor of kynureninase. The compound had a significant inhibitory effect on kynureninase from both rat and human, giving a K-i of 100 nM. It was thus found that removal of the aryl amino group coupled with a reduction of the carbonyl group at position 7 of the alanine side chain greatly enhanced potency of the inhibitor. (C) 2002 Elsevier Science Ltd. All rights reserved.