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Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors.

  • Jakob Nilsson
  • Ritha Gidlöf
  • Elsebet Østergaard Nielsen
  • Tommy Liljefors
  • Mogens Nielsen
  • Olov Sterner
Publishing year: 2011
Language: English
Pages: 111-121
Publication/Series: Bioorganic & Medicinal Chemistry
Volume: 19
Issue: 1
Document type: Journal article
Publisher: Elsevier

Abstract english

Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K(i) values of around 0.20nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat α(1)β(3)γ(2), α(2)β(3)γ(2), α(3)β(3)γ(2), and α(5)β(3)γ(2) subtypes, and displayed selectivity for the α(1)β(3)γ(2) isoform.


  • Organic Chemistry


  • ISSN: 0968-0896
Olov Sterner
E-mail: olov [dot] sterner [at] science [dot] lu [dot] se


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