Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors
Research output: Contribution to journal › Journal article › Research › peer-review
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 GABA(A) 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 alpha- and a gamma-subunit in the GABA(A) receptor, selected compounds were tested on the alpha(1)beta(2)gamma(2s), alpha(2)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes. The 3-acyl-4-quinolones display various degrees of selectivity for alpha(1)- versus alpha(2)- and alpha(3)-containing receptors, and high-affinity ligands essentially selective for alpha(1) over alpha(3) were developed.
Original language | English |
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Journal | Bioorganic & Medicinal Chemistry |
Volume | 16 |
Issue number | 14 |
Pages (from-to) | 6936-6948 |
ISSN | 0968-0896 |
DOIs | |
Publication status | Published - 2008 |
Bibliographical note
Keywords: 4-Quinolones; Animals; Benzodiazepines; Binding Sites; Ligands; Protein Binding; Protein Subunits; Receptors, GABA-A; Structure-Activity Relationship
- Former Faculty of Pharmaceutical Sciences
Research areas
ID: 10159584