Modulators of the kynurenine pathway of triptophan metabolism. Synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, the first potent and selective kynurenine aminotransferse II (KAT II) inhibitor

(S)-4-(Ethylsulfonyl)benzoylalanine, here reported, is the first selective, synthetic KAT II inhibitor described so far and should prove to be a useful tool for elucidating pivotal aspects of KYNA neurobiology, including the role of KYNA as an endogenous modulator of glutamatergic and cholinergic neurotransmission. After appropriate modification, (S)-4-(ethylsulfonyl)benzoylalanine or a congener may also be capable of transiently lowering KYNA levels in the human brain. The expected result, that is, increased activity of NMDA and a7* nicotinic receptors, may be beneficial toward cognitive processes in normal individuals and is a desirable goal in the treatment of catastrophic brain diseases such as Alzheimer’s disease and schizophrenia.