Design, synthesis and pharmacological evaluation of 4-(piperazin-1-yl methyl)-N₁-arylsulfonyl indole derivatives as 5-HT₆ receptor ligands

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7431-5. doi: 10.1016/j.bmcl.2012.10.057. Epub 2012 Oct 17.

Abstract

4-(Piperazin-1-yl methyl)-N(1)-arylsulfonyl indole derivatives were designed and synthesized as 5-HT(6) receptor (5-HT(6)R) ligands. The lead compound 6a, from this series shows potent in vitro binding affinity, good PK profile, no CYP liabilities and activity in animal models of cognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • HEK293 Cells
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Ligands
  • Male
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship

Substances

  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Indoles
  • Ligands
  • Receptors, Serotonin
  • serotonin 6 receptor
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A