The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors

…, M Jacobson, B Jones, S Munshi, D Pascarella…

文献索引：Sparey, Tim; Abeywickrema, Pravien; Almond, Sarah; Brandon, Nick; Byrne, Noel; Campbell, Alister; Hutson, Pete H.; Jacobson, Marlene; Jones, Brian; Munshi, Sanjeev; Pascarella, Danette; Pike, Andrew; Prasad, G. Sridhar; Sachs, Nancy; Sakatis, Melanie; Sardana, Vinod; Venkatraman, Shankar; Young, Mary Beth Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 11 p. 3386 - 3391

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被引用次数: 52

摘要

The 'NMDA hypofunction hypothesis of schizophrenia'can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.