γ‑Aminobutyric Acid(C) (GABAC) Selective Antagonists Derived from the Bioisosteric Modification of 4‑Aminocyclopent-1-enecarboxylic Acid: Amides and Hydroxamates

Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This pro...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2013-07, Vol.56 (13), p.5626-5630
Hauptverfasser:	Locock, Katherine E. S, Yamamoto, Izumi, Tran, Priscilla, Hanrahan, Jane R, Chebib, Mary, Johnston, Graham A. R, Allan, Robin D
Format:	Artikel
Sprache:	eng
Schlagworte:	Amides - chemical synthesis Amides - chemistry Amides - pharmacology Animals Binding, Competitive Chemistry, Pharmaceutical - methods Cyclopentanes - chemistry Cyclopentanes - pharmacology Female GABA Antagonists - chemistry GABA Antagonists - pharmacology Humans Hydroxamic Acids - chemical synthesis Hydroxamic Acids - chemistry Hydroxamic Acids - pharmacology Membrane Potentials - drug effects Models, Chemical Models, Molecular Molecular Structure Oocytes - drug effects Oocytes - metabolism Oocytes - physiology Patch-Clamp Techniques Protein Structure, Tertiary Receptors, GABA - chemistry Receptors, GABA - genetics Receptors, GABA - metabolism Xenopus laevis
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This provides evidence that a zwitterionic structure is not essential for GABAC antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm4006548