Abstract
Here we report the design, synthesis, and 5-HT(7) receptor affinity of a set of 1-(3-biphenyl)- and 1-(2-biphenyl)piperazines. The effect on 5-HT(7) affinity of various substituents on the second (distal) phenyl ring was analyzed. Several compounds showed 5-HT(7) affinities in the nanomolar range and >100-fold selectivity over 5-HT(1A) and adrenergic α(1) receptors. 1-[2-(4-Methoxyphenyl)phenyl]piperazine (9a) showed 5-HT(7) agonist properties in a guinea pig ileum assay but blocked 5-HT-mediated cAMP accumulation in 5-HT(7)-expressing HeLa cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Guinea Pigs
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HeLa Cells
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Humans
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Ileum / drug effects
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Ileum / metabolism
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Ligands
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Models, Molecular
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Molecular Weight
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Piperazine
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Piperazines / chemical synthesis
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Piperazines / chemistry*
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Piperazines / metabolism
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Piperazines / pharmacology*
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Protein Conformation
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Receptors, Adrenergic, alpha-1 / metabolism
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Receptors, Serotonin / chemistry
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / chemical synthesis
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Serotonin Antagonists / chemistry*
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Serotonin Antagonists / metabolism
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Serotonin Antagonists / pharmacology*
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Serotonin Receptor Agonists / chemical synthesis
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Serotonin Receptor Agonists / chemistry*
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Serotonin Receptor Agonists / metabolism
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Serotonin Receptor Agonists / pharmacology*
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Ligands
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Piperazines
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Receptors, Adrenergic, alpha-1
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Receptors, Serotonin
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Serotonin Antagonists
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Serotonin Receptor Agonists
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serotonin 7 receptor
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Piperazine