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The synthesis and SAR of 2-arylsulfanyl-phenyl piperazinyl acetic acids as glyT-1 inhibitors.

Abstract：

:Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC(50)=150 nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2-4.6 mg/kg s.c.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Smith G,Ruhland T,Mikkelsen G,Andersen K,Christoffersen CT,Alifrangis LH,Mørk A,Wren SP,Harris N,Wyman BM,Brandt G

doi

10.1016/j.bmcl.2004.05.043

subject

Has Abstract

pub_date

2004-08-02 00:00:00

pages

4027-30

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960894X04006948

journal_volume

14

pub_type

杂志文章

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