Novel 4-(piperidin-4-yl)-1-hydroxypyrazoles as gamma-aminobutyric acidA receptor ligands: synthesis, pharmacology, and structure-activity relationships

Research output: Contribution to journalJournal articleResearchpeer-review

Henriette A Møller, Tommy Sander, Jesper Langgaard Kristensen, Birgitte Nielsen, Jacob Krall, Marianne Lerbæk Bergmann, Bolette Christiansen, Thomas Balle, Anders Asbjørn Jensen, Bente Flensborg Frølund

A series of substituted 1-hydroxypyrazole analogues of the GABA(A) receptor partial agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL) have been synthesized and pharmacologically characterized. Several of the analogues displayed K(i) in the low nanomolar range at the native GABA(A) receptors and potent antagonism of the alpha(1)beta(2)gamma(2) receptor. It appears that several regions situated in proximity to the core of the orthosteric binding site of the GABA(A) receptor are able to accommodate large hydrophobic substituents.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume53
Issue number8
Pages (from-to)3417-3421
ISSN0022-2623
DOIs
Publication statusPublished - 2010

Bibliographical note

Keywords: Animals; Cell Line; GABA Antagonists; GABA Plasma Membrane Transport Proteins; Humans; Hydrophobicity; Ligands; Membrane Potentials; Models, Molecular; Piperidines; Pyrazoles; Rats; Receptors, GABA-A; Structure-Activity Relationship; Synaptic Membranes

ID: 20197322