Novel glycine transporter type-2 reuptake inhibitors. Part 1: α-amino acid derivatives

Add time:07/24/2019    Source:sciencedirect.com

A variety of α-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) was evaluated. An array of substituents at the chiral center was studied and overall, l-phenylalanine was identified as the preferred amino acid residue. Compounds prepared from l-amino acids were more potent GlyT-2 inhibitors than analogs derived from the corresponding d-amino acids. Introducing an achiral amino acid such as glycine, or incorporating geminal substitution in the α-position, led to a significant reduction in GlyT-2 inhibitory properties.

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