The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter

  • Bioorg Med Chem Lett. 2009 Jun 1;19(11):2974-6. doi: 10.1016/j.bmcl.2009.04.035.
John A Lowe 3rd  1 ,  Xinjun Hou ,  Christopher Schmidt ,  F David Tingley 3rd ,  Stan McHardy ,  Monica Kalman ,  Shari Deninno ,  Mark Sanner ,  Karen Ward ,  Lorraine Lebel ,  Don Tunucci ,  James Valentine ,  Brian S Bronk ,  Eric Schaeffer
Affiliations
  • 1. Pfizer Global Research and Development, Groton, CT 06340, United States. [email protected]
PMID: 19410451 DOI: 10.1016/j.bmcl.2009.04.035
Abstract

The type 1 glycine transporter plays an important in regulating homeostatic glycine levels in the brain that are relevant to the activation of the NMDA Receptor by the excitatory neurotransmitter glutamate. We describe herein the structure-activity relationships (SAR) of a structurally novel class of GlyT1 inhibitors following on a lead derived from high throughput screening, which shows good selectivity for GlyT1 and potent activity in elevating CSF levels of glycine.

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