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ID: ALA2401667

Journal: Eur J Med Chem

Title: Synthesis of N-substituted acyclic β-amino acids and their investigation as GABA uptake inhibitors.

Authors: Sitka I, Allmendinger L, Fülep G, Höfner G, Wanner KT.

Abstract: In this publication, we describe the synthesis of new inhibitors for the GABA transporter subtypes GAT1 and especially GAT3. We started with 3-aminopropanoic acid possessing a distinct preference for GAT3 in comparison to GAT1 and furthermore its homolog 3-aminobutanoic acid. A series of respective N-substituted amino acids was synthesized by selective N-monoalkylation of these parent structures with 6 different arylalkyl alcohols via a Mitsunobu-type reaction. The resulting compounds were investigated for their inhibitory potency GABA transporter subtypes. Among all tested compounds the 4,4-diphenylbut-3-enyl substituted 3-aminobutanoic acid (rac)-6b showed highest potency with a pIC50 value of 5.34 at GAT1. Unfortunately, the expected GAT3 potency for 2-[tris(4-methoxyphenyl)methoxy]ethyl substituted derivatives was not as high as observed for the respective nipecotic acid derivatives.

CiteXplore: 23770450

DOI: 10.1016/j.ejmech.2013.04.063