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

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 .