Modulators of the Kynurenine Pathway of Tryptophan Metabolism: Synthesis and Preliminary Biological Evaluation of (S)-4-(Ethylsulfonyl)benzoylalanine,a Potent and Selective Kynurenine Aminotransferase II (KAT II) Inhibitor

摘要

In mammals,most non-proteinogenic L-tryptophan is metabolized by a complex enzymatic cascade known as the kynurenine pathway (KP,Scheme 1),which ultimately leads to the production of NAD.The KP has received considerable interest over the last decade since several of its components are endowed with neuroactive properties.Thus,in a branch of the pathway initiated by the rate-limiting enzyme kynurenine 3-hydroxy-lase,the central metabolite kynurenine (KYN,1) is transformed into the pro-excitotoxic free-radical generator 3-hydroxykynure-nine (3-HK,2) and then further into the excitotoxin quinolinic acid (QUIN,3).