2-Amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid; a potent inhibitor of rat and recombinant human kynureninase

Abstract

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.