Abstract
As part of our efforts to develop agents for CNS diseases, we have been focused on the 5-HT(6) receptor in order to identify potent and selective ligands for cognitive enhancement. Herein we report the identification of a novel series of 5-piperazinyl-3-sulfonylindazoles as potent and selective 5-HT(6) antagonists. The synthesis, SAR, and pharmacokinetic and pharmacological activities of some of the compounds including 3-(naphthalen-1-ylsulfonyl)-5-(piperazin-1-yl)-1H-indazole (WAY-255315 or SAM-315) will be described.
MeSH terms
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Acetylcholine / metabolism
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Animals
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Biological Availability
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Brain / metabolism
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Glutamic Acid / metabolism
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HeLa Cells
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Humans
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Indazoles / chemical synthesis*
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Indazoles / pharmacokinetics
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Indazoles / pharmacology
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Ligands
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Nootropic Agents / chemical synthesis*
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Nootropic Agents / pharmacokinetics
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Nootropic Agents / pharmacology
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Piperazines / chemical synthesis*
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Piperazines / pharmacokinetics
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Piperazines / pharmacology
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Rats
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Receptors, Serotonin / metabolism*
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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
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Sulfones / chemical synthesis*
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Sulfones / pharmacokinetics
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Sulfones / pharmacology
Substances
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3-(naphthalen-1-ylsulfonyl)-5-(piperazin-1-yl)-1H-indazole
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Indazoles
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Ligands
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Nootropic Agents
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Piperazines
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Receptors, Serotonin
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Serotonin Antagonists
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Sulfones
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serotonin 6 receptor
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Glutamic Acid
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Acetylcholine