The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.
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Sparey T, Abeywickrema P, Almond S, Brandon N, Byrne N, Campbell A, Hutson PH, Jacobson M, Jones B, Munshi S, Pascarella D, Pike A, Prasad GS, Sachs N, Sakatis M, Sardana V, Venkatraman S, Young MB
The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3386-91. doi: 10.1016/j.bmcl.2008.04.020. Epub 2008 Apr 13.
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- 18455394 [ View in PubMed]
- Abstract
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.