Abstract
3-Quinolinecarboxamides have been synthesized and evaluated for their binding to the human NK(1) receptor. Several secondary amide derivatives show NK(1) receptor affinity in the picomolar range. The most active compound, hydroxymethylcarboxamide 3h showing an IC(50) value in the subpicomolar range, behaved as an agonist of NK(1) receptor in endothelial cell proliferation, inositol phosphate turnover, and NO-mediated cyclic GMP accumulation, thus proving it to be the first non-peptide NK(1) receptor agonist showing very high potency.
MeSH terms
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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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Cattle
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Cell Division / drug effects
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Cyclic GMP / biosynthesis
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Humans
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In Vitro Techniques
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Inositol Phosphates / metabolism
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Nitric Oxide / metabolism
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / pharmacology
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Receptors, Neurokinin-1 / agonists*
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Structure-Activity Relationship
Substances
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Amides
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Inositol Phosphates
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Quinolines
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Receptors, Neurokinin-1
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Nitric Oxide
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Cyclic GMP