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Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors.

In English

Författare

  • Erik Lager
  • Jakob Nilsson
  • Elsebet Østergaard Nielsen
  • Mogens Nielsen
  • Tommy Liljefors
  • Olov Sterner

Summary, in English

The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABAA receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an α- and a γ-subunit in the GABAA receptor, selected compounds were tested on the α1β2γ2s, α2β2γ2s and α3β2γ2s GABAA receptor subtypes. The 3-acyl-4-quinolones display various degrees of selectivity for α1- versus α2- and α3-containing receptors, and high-affinity ligands essentially selective for α1 over α3 were developed.

Publiceringsår

2008

Språk

Engelska

Sidor

6936-6948

Publikation/Tidskrift/Serie

Bioorganic & Medicinal Chemistry

Volym

16

Issue

14

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Organic Chemistry

Nyckelord

  • 3-Acyl-1
  • 4-dihydro-4-oxoquinolines
  • Benzodiazepine binding site
  • GABAA receptor
  • GABAA receptor subtypes
  • Pharmacophore model

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0968-0896