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

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.