Abstract
On the basis of the previously reported clinical candidate, SSA-426 (1), a series of related 2-piperazin-1-ylquinoline derivatives 3-16 were synthesized and evaluated as dual-acting serotonin (5-HT) reuptake inhibitors and 5-HT1A receptor antagonists. In particular, compound 7 exhibits potent functional activities at both the 5-HT transporter and 5-HT1A receptor, good selectivity over the alpha1-adrenergic and dopaminergic receptors, acceptable pharmacokinetic properties, and a favorable in vivo profile.
MeSH terms
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Animals
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Antidepressive Agents / pharmacology
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CHO Cells
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Cricetinae
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Cricetulus
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Cytochrome P-450 Enzyme Inhibitors
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Humans
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Microdialysis
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Piperazines / chemical synthesis*
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Piperazines / pharmacology
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Quinolines / chemical synthesis*
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Quinolines / pharmacology
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Rats
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Receptors, Adrenergic, alpha-1 / metabolism
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Receptors, Dopamine / metabolism
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Selective Serotonin Reuptake Inhibitors / chemical synthesis*
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin 5-HT1 Receptor Antagonists*
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / pharmacokinetics
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Serotonin Antagonists / pharmacology
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Structure-Activity Relationship
Substances
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Antidepressive Agents
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Cytochrome P-450 Enzyme Inhibitors
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Piperazines
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Quinolines
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Receptors, Adrenergic, alpha-1
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Receptors, Dopamine
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin Antagonists
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Serotonin Uptake Inhibitors