Abstract
A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC(50)=1.9 nM for LXRbeta and EC(50)=34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists.
MeSH terms
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters / biosynthesis
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ATP-Binding Cassette Transporters / genetics
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology
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Animals
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Cell Line
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Crystallography, X-Ray
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DNA-Binding Proteins / agonists*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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Gene Expression Regulation / drug effects
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Kinetics
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Ligands
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Liver X Receptors
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Mice
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Models, Molecular
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Orphan Nuclear Receptors
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Quinolines / chemical synthesis
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Quinolines / chemistry
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Quinolines / pharmacology*
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Transcriptional Activation / drug effects
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Transfection
Substances
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters
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Amides
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DNA-Binding Proteins
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Ligands
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Liver X Receptors
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Orphan Nuclear Receptors
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Quinolines
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Receptors, Cytoplasmic and Nuclear