5-Piperazinyl-3-sulfonylindazoles as Potent and Selective 5-Hydroxytryptamine-6 Antagonists

As part of our efforts to develop agents for CNS diseases, we have been focused on the 5-HT6 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-HT6...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2010-11, Vol.53 (21), p.7639-7646
Main Authors: Liu, Kevin G, Robichaud, Albert J, Bernotas, Ronald C, Yan, Yinfa, Lo, Jennifer R, Zhang, Mei-Yi, Hughes, Zoe A, Huselton, Christine, Zhang, Guo Ming, Zhang, Jean Y, Kowal, Dianne M, Smith, Deborah L, Schechter, Lee E, Comery, Thomas A
Format: Article
Language:English
Subjects:
Acetylcholine - metabolism
Animals
Biological Availability
Brain - metabolism
Glutamic Acid - metabolism
HeLa Cells
Humans
Indazoles - chemical synthesis
Indazoles - pharmacokinetics
Indazoles - pharmacology
Ligands
Nootropic Agents - chemical synthesis
Nootropic Agents - pharmacokinetics
Nootropic Agents - pharmacology
Piperazines - chemical synthesis
Piperazines - pharmacokinetics
Piperazines - pharmacology
Rats
Receptors, Serotonin - metabolism
Serotonin Antagonists - chemical synthesis
Serotonin Antagonists - pharmacokinetics
Serotonin Antagonists - pharmacology
Structure-Activity Relationship
Sulfones - chemical synthesis
Sulfones - pharmacokinetics
Sulfones - pharmacology
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Summary:As part of our efforts to develop agents for CNS diseases, we have been focused on the 5-HT6 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-HT6 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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm1007825