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ID: ALA1146043
Journal: Bioorg Med Chem Lett
Title: The synthesis and SAR of 2-arylsulfanylphenyl-1-oxyalkylamino acids as GlyT-1 inhibitors.
Authors: Smith G, Mikkelsen G, Eskildsen J, Bundgaard C.
Abstract: Elevation of glycine levels by inhibition of the glycine transporter-1 (GlyT-1) and activation of the NMDA receptor is a potential strategy for the treatment of schizophrenia. A novel series of 2-arylsulfanylphenyl-1-oxyalkyl amino acids have been identified. The most prominent member of this series S-1-{2-[3-(3-fluoro-phenylsulfanyl)biphenyl-4-yloxy]ethyl}pyrrolidine-2-carboxylic acid (38) is a potent GlyT-1 inhibitor (IC50=59 nM). In vitro and in vivo assessment of CNS exposure indicates this compound is a likely substrate for active efflux transporters.
CiteXplore: 16725323