N-Benzyl-N-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amines as selective dual serotonin/noradrenaline reuptake inhibitors

Bioorg Med Chem Lett. 2007 Apr 1;17(7):2022-5. doi: 10.1016/j.bmcl.2007.01.020. Epub 2007 Jan 19.

Abstract

A series of N-benzyl-N-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amine monoamine reuptake inhibitors are described. Selective dual 5-HT and NA reuptake inhibition was achieved, and analogues with weak CYP2D6 inhibition, good human in vitro metabolic stability and wide ligand selectivity, such as 12b, were identified.

MeSH terms

  • Amines / chemistry
  • Chemistry, Pharmaceutical / methods*
  • Cytochrome P-450 CYP2D6 Inhibitors*
  • Drug Design
  • Ether-A-Go-Go Potassium Channels / chemistry
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Models, Chemical
  • Molecular Conformation
  • Norepinephrine / antagonists & inhibitors*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Serotonin Uptake Inhibitors / chemical synthesis*
  • Serotonin Uptake Inhibitors / chemistry
  • Serotonin Uptake Inhibitors / pharmacology

Substances

  • Amines
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Ether-A-Go-Go Potassium Channels
  • KCNH1 protein, human
  • Ligands
  • Pyrrolidines
  • Serotonin Uptake Inhibitors
  • Norepinephrine