Synthesis and Biological Evaluation of d Amino Acid Oxidase Inhibitors (original) (raw)

Abstract

D-Amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids including D-serine, a full agonist at the glycine site of the NMDA receptor. A series of benzo[d]isoxazol-3-ol derivatives were synthesized and evaluated as DAAO inhibitors. Among them, 5-chlorobenzo[d]isoxazol-3-ol (CBIO) potently inhibited DAAO with an IC50 in the submicromolar range. Oral administration of CBIO in conjunction with D-serine enhanced the plasma and brain levels of D-serine in rats compared to the oral administration of D-serine alone.

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