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.
Walsh
Harold A
HA
School of Chemistry, University of St Andrews, St Andrews, Fife KY16 9ST, UK.
Leslie
Pauline L
PL
O'Shea
Karen C
KC
Botting
Nigel P
NP
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D006885:Hydroxybutyrates / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D010654:Phenylbutyrates / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
C456405:2-amino-4-(3'-hydroxyphenyl)-4-hydroxybutanoic acid; D004791:Enzyme Inhibitors; D006885:Hydroxybutyrates; D010654:Phenylbutyrates; D011994:Recombinant Proteins; D006867:Hydrolases; C021480:kynureninase