Ferraris Dana, Duvall Bridget, Ko Yao-Sen, Thomas Ajit G, Rojas Camilo, Majer Pavel, Hashimoto Kenji, Tsukamoto Takashi
MGI Pharma, Inc.
J Med Chem. 2008 Jun 26;51(12):3357-9. doi: 10.1021/jm800200u. Epub 2008 May 29.
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-chloro-benzo[ 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.
D-氨基酸氧化酶（DAAO）催化包括D-丝氨酸在内的D-氨基酸的氧化反应，D-丝氨酸是N-甲基-D-天冬氨酸受体甘氨酸位点的完全激动剂。合成了一系列苯并[d]异恶唑-3-醇衍生物，并对其作为DAAO抑制剂进行了评估。其中，5-氯-苯并[d]异恶唑-3-醇（CBIO）能有效抑制DAAO，其半数抑制浓度（IC50）在亚微摩尔范围内。与单独口服D-丝氨酸相比，CBIO与D-丝氨酸联合口服可提高大鼠血浆和脑内D-丝氨酸水平。
