4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling

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4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling. / Lager, Erik; Andersson, P; Nilsson, Jakob; Pettersson, I; Nielsen, EO; Nielsen, M; Sterner, Olov; Liljefors, T.

In: Journal of Medicinal Chemistry, Vol. 49, No. 8, 2006, p. 2526-2533.

Research output: Contribution to journalArticle

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Lager, Erik ; Andersson, P ; Nilsson, Jakob ; Pettersson, I ; Nielsen, EO ; Nielsen, M ; Sterner, Olov ; Liljefors, T. / 4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 8. pp. 2526-2533.

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TY - JOUR

T1 - 4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling

AU - Lager, Erik

AU - Andersson, P

AU - Nilsson, Jakob

AU - Pettersson, I

AU - Nielsen, EO

AU - Nielsen, M

AU - Sterner, Olov

AU - Liljefors, T

N1 - 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)

PY - 2006

Y1 - 2006

N2 - The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.

AB - The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.

U2 - 10.1021/jm058057p

DO - 10.1021/jm058057p

M3 - Article

VL - 49

SP - 2526

EP - 2533

JO - Journal of Medicinal and Pharmaceutical Chemistry

JF - Journal of Medicinal and Pharmaceutical Chemistry

SN - 1520-4804

IS - 8

ER -