5-Piperazinyl-3-sulfonylindazoles as potent and selective 5-hydroxytryptamine-6 antagonists.

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.

• Authors: Kevin G Liu, Albert J Robichaud, Ronald C Bernotas, Yinfa Yan, Jennifer R Lo, Mei-Yi Zhang, Zoe A Hughes, Christine Huselton, Guo Ming Zhang, Jean Y Zhang, Dianne M Kowal, Deborah L Smith, Lee E Schechter, Thomas A Comery
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 53 Issue 21 Pg. 7639-46 (Nov 11 2010) ISSN: 1520-4804 [Electronic] United States
• PMID: 20932009 (Publication Type: Journal Article)

Chemical References

• 3-(naphthalen-1-ylsulfonyl)-5-(piperazin-1-yl)-1H-indazole
• Indazoles
• Ligands
• Nootropic Agents
• Piperazines
• Receptors, Serotonin
• Serotonin Antagonists
• Sulfones
• serotonin 6 receptor
• Glutamic Acid
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Animals
• Biological Availability
• Brain (metabolism)
• Glutamic Acid (metabolism)
• HeLa Cells
• Humans
• Indazoles (chemical synthesis, pharmacokinetics, pharmacology)
• Ligands
• Nootropic Agents (chemical synthesis, pharmacokinetics, pharmacology)
• Piperazines (chemical synthesis, pharmacokinetics, pharmacology)
• Rats
• Receptors, Serotonin (metabolism)
• Serotonin Antagonists (chemical synthesis, pharmacokinetics, pharmacology)
• Structure-Activity Relationship
• Sulfones (chemical synthesis, pharmacokinetics, pharmacology)