2. Academic Validation
  3. Novel 4-(piperidin-4-yl)-1-hydroxypyrazoles as gamma-aminobutyric acid(A) receptor ligands: synthesis, pharmacology, and structure-activity relationships

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

  • J Med Chem. 2010 Apr 22;53(8):3417-21. doi: 10.1021/jm100106r.
Henriette A Møller 1,  Tommy Sander,  Jesper L Kristensen,  Birgitte Nielsen,  Jacob Krall,  Marianne L Bergmann,  Bolette Christiansen,  Thomas Balle,  Anders A Jensen,  Bente Frølund
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2 Universitetsparken, DK 2100 Copenhagen.
PMID: 20355712 DOI: 10.1021/jm100106r
Abstract

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.

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