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

Bioorg Med Chem Lett. 2002 Feb 11;12(3):361-3. doi: 10.1016/s0960-894x(01)00758-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrolases / antagonists & inhibitors*
  • Hydroxybutyrates / chemical synthesis*
  • Hydroxybutyrates / pharmacology*
  • Kinetics
  • Liver / enzymology
  • Phenylbutyrates / chemical synthesis*
  • Phenylbutyrates / pharmacology*
  • Rats
  • Recombinant Proteins / antagonists & inhibitors

Substances

  • 2-amino-4-(3'-hydroxyphenyl)-4-hydroxybutanoic acid
  • Enzyme Inhibitors
  • Hydroxybutyrates
  • Phenylbutyrates
  • Recombinant Proteins
  • Hydrolases
  • kynureninase