Synthesis and biological evaluation of α- and β-hydroxy substituted amino acid derivatives as potential mGAT1–4 inhibitors

In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced eit her at the amino nitrogen atom or at the alcohol function. Several of the synthesized compounds were found to exhibit similar inhibitory activity at the GAT subtypes mGAT2, mGAT3, and mGAT4, respectively, as compared with the reference N-butylnipecotic acid. Hence, these compounds might serve as sta rting point for future developments of more complex GAT inhibitors.

Source: Medicinal Chemistry Research - May 7, 2020 Category: Chemistry Source Type: research