Abstract
The synthesis and SAR of tolylamines with 5-HT(6) receptor antagonist activity is presented. The amine, core aromatic, peripheral aromatic, and ether linker moieties of HTS hit 1 were modulated and the effect on potency at 5-HT(6) examined. Tolylpiperidine ether 9h was found to possess desirable pharmacokinetic (PK) properties, and was also shown to enhance cognition in the rat novel object recognition paradigm.
MeSH terms
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Amines / chemistry*
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Animals
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Chemistry, Organic / methods
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Chemistry, Pharmaceutical / methods
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Drug Design
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Ethers / chemistry
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Inhibitory Concentration 50
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Kinetics
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Models, Chemical
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Rats
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Receptors, Serotonin / chemistry*
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Serotonin Receptor Agonists / chemical synthesis*
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Serotonin Receptor Agonists / chemistry
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Serotonin Receptor Agonists / pharmacology
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Structure-Activity Relationship
Substances
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Amines
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Ethers
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Receptors, Serotonin
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Serotonin Receptor Agonists
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serotonin 6 receptor