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ID: ALA1649378

Journal: Eur J Med Chem

Title: Synthesis and biological evaluation of new derivatives of 2-substituted 4-hydroxybutanamides as GABA uptake inhibitors.

Authors: Kulig K, Więckowski K, Więckowska A, Gajda J, Pochwat B, Höfner GC, Wanner KT, Malawska B.

Abstract: This study presents the synthesis of novel substituted 4-hydroxybutanamides and their influence on the activity of murine GABA transport proteins GAT1-GAT4. The active compounds, derivatives of N-arylalkyl-2-(4-diphenylmethylpiperazin-1-yl)-4-hydroxybutyramide, are characterized by pIC(50) values in range of 3.92-5.06 and by slight subtype-selectivity. Among them N-4-chlorobenzylamide was the most potent GAT inhibitor (mGAT3), while N-benzylamide was the most active in GAT1-binding assay (pK(i) = 4.96). The results pointed out that benzhydryl and benzylamide moieties are crucial for the activity of this class of compounds as murine GAT inhibitors.

CiteXplore: 21111516

DOI: 10.1016/j.ejmech.2010.11.001