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

Research output: Contribution to journalArticle


title = "Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors.",
abstract = "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.",
author = "Jakob Nilsson and Ritha Gidl{\"o}f and Nielsen, {Elsebet {\O}stergaard} and Tommy Liljefors and Mogens Nielsen and Olov Sterner",
note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)",
year = "2011",
doi = "10.1016/j.bmc.2010.11.050",
language = "English",
volume = "19",
pages = "111--121",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier",
number = "1",