2. Academic Validation
  3. 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

  • Bioorg Med Chem Lett. 2008 Jun 1;18(11):3386-91. doi: 10.1016/j.bmcl.2008.04.020.
Tim Sparey 1,  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
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. tim_sparey@merck.com
PMID: 18455394 DOI: 10.1016/j.bmcl.2008.04.020
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.

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