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

Abstract Several β- and γ-amino acid derivatives were prepared as glycine transport inhibitors and their ability to block the uptake of [ 14 C]-glycine in COS7 cells transfected with human glycine transporter-2 ( h GlyT-2) were evaluated. A range of lipophilic side chains were tolerated in the β-amino acid series (i.e., Ph, CH 2 Ph, CH(CH 3 ) 2 , and CH 2 CH(CH 3 ) 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.