Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists

J Med Chem. 2005 Jan 27;48(2):353-6. doi: 10.1021/jm049243i.

Abstract

5-Arylsulfonylamido-3-(pyrrolidin-2-ylmethyl)-1H-indoles have been identified as high-affinity 5-HT(6) receptor ligands. Within this class, several of the (R)-enantiomers were potent agonists having EC(50) values of 1 nM or less and functioning as full agonists while the (S)-enantiomers displayed moderate antagonist activity.

MeSH terms

  • Cyclic AMP / agonists
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / biosynthesis
  • HeLa Cells
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • Receptors, Serotonin / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology

Substances

  • Indoles
  • Pyrrolidines
  • Receptors, Serotonin
  • Sulfonamides
  • serotonin 6 receptor
  • Cyclic AMP