Abstract
A series of 3-imino-2-indolones are the first published, high-affinity antagonists of the galanin GAL3 receptor. One example, 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for GAL3 over a broad panel of targets, including GAL1 and GAL2. Compound 9 was also shown to be an antagonist in a human GAL3 receptor functional assay (Kb=29 nM).
MeSH terms
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Animals
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Binding, Competitive
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Brain / metabolism
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COS Cells
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Chlorocebus aethiops
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Cyclic AMP / biosynthesis
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Humans
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Imines / chemical synthesis*
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Imines / pharmacokinetics
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Imines / pharmacology
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Indoles / chemical synthesis*
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Indoles / pharmacokinetics
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Indoles / pharmacology
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Ligands
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Radioligand Assay
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Rats
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Receptor, Galanin, Type 1 / drug effects
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Receptor, Galanin, Type 2 / drug effects
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Receptor, Galanin, Type 3 / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Imines
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Indoles
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Ligands
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Receptor, Galanin, Type 1
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Receptor, Galanin, Type 2
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Receptor, Galanin, Type 3
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Cyclic AMP
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1,3-dihydro-1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-2H-indol-2-one