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D-型氨基酸氧化酶(D-Amino acid oxidase,DAAO)抑制剂可以阻止D-型氨基酸(主要是D-型丝氨酸)的降解和过氧化氢的生成,在治疗精神分裂症阴性症状和认知障碍与镇痛等方面均表现出较好的疗效。从第一个DAAO抑制剂芳香羧酸类的苯甲酸到经过烯醇互变的α-羟基酮喹类抑制剂喹诺林-2,3-二酮,DAAO抑制剂结构上总共经历了3代变化,抑制剂与酶之间的相互作用模式逐渐加强,其抑制活性升高了数万倍,脂溶性增加,酸性减弱,理化性质逐渐优化。本文就近10年DAAO抑制剂的结构发展与生物活性之间的关系进行综述。
D-Amino acid oxidase (DAO) inhibitors can prevent the degradation of D-type amino acids (mainly D-type serine) and the formation of hydrogen peroxide. In the treatment of negative symptoms and cognition of schizophrenia Obstacles and analgesia showed good results. From the first DAAO inhibitor, an aromatic carboxylic acid, to quinolyn-2,3-dione, an enol-interconverted α-hydroxy ketoquine inhibitor, the DAAO inhibitor structurally lasted a total of three generations Changes, inhibitor and enzyme interaction between the mode gradually strengthened, the inhibitory activity increased tens of thousands of times, fat-soluble increase, acidic weakened, gradually optimized physical and chemical properties. This review summarizes the relationship between the structural development and bioactivity of DAAO inhibitors in the recent 10 years.