- The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.
The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.
Bioorganic & medicinal chemistry letters (2008-05-06)
Tim Sparey, Pravien Abeywickrema, Sarah Almond, Nick Brandon, Noel Byrne, Alister Campbell, Pete H Hutson, Marlene Jacobson, Brian Jones, Sanjeev Munshi, Danette Pascarella, Andrew Pike, G Sridhar Prasad, Nancy Sachs, Melanie Sakatis, Vinod Sardana, Shankar Venkatraman, Mary Beth Young
PMID18455394
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.
MATERIALS