Novel glycine transporter type-2 reuptake inhibitors. Part 2: β- and γ-amino acid derivatives Original Research Article

Several β- and γ-amino acid derivatives were prepared as glycine transport inhibitors and their ability to block the uptake of [14C]-glycine in COS7 cells transfected with human glycine transporter-2 (hGlyT-2) were evaluated. A range of lipophilic side chains were tolerated in the β-amino acid series (i.e., Ph, CH2Ph, CH(CH3)2, and CH2CH(CH3)2). In the γ-amino acid series, minimal differences in potency were observed between the α,β-unsaturated analogs and the corresponding saturated derivatives. In both series, a 4-biphenyl or 4-phenoxyphenyl substituent appended to the urea or cyanogunaidine moiety was necessary for in vitro activity.