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

J Med Chem. 2010 Nov 11;53(21):7639-46. doi: 10.1021/jm1007825.

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

  • 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

Substances

  • 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