1-(2-Phenoxyphenyl)methanamines: SAR for dual serotonin/noradrenaline reuptake inhibition, metabolic stability and hERG affinity

Gavin A Whitlock; Julian Blagg; Paul V Fish

doi:10.1016/j.bmcl.2007.11.080

1-(2-Phenoxyphenyl)methanamines: SAR for dual serotonin/noradrenaline reuptake inhibition, metabolic stability and hERG affinity

Bioorg Med Chem Lett. 2008 Jan 15;18(2):596-9. doi: 10.1016/j.bmcl.2007.11.080.

Authors

Gavin A Whitlock¹, Julian Blagg, Paul V Fish

Affiliation

¹ Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. gavin.whitlock@pfizer.com

PMID: 18240382
DOI: 10.1016/j.bmcl.2007.11.080

Abstract

A novel series of 1-(2-phenoxyphenyl)methanamines is disclosed, which possess selective dual 5-HT and NA reuptake pharmacology. Analogues with good human in vitro metabolic stability, hERG selectivity and passive membrane permeability were identified.

MeSH terms

Amines / chemistry*
Amines / pharmacology*
Cell Membrane Permeability / drug effects
ERG1 Potassium Channel
Ether-A-Go-Go Potassium Channels / metabolism*
Humans
In Vitro Techniques
Molecular Conformation
Neurotransmitter Uptake Inhibitors / chemistry*
Neurotransmitter Uptake Inhibitors / pharmacology*
Norepinephrine / metabolism*
Selective Serotonin Reuptake Inhibitors / chemistry*
Selective Serotonin Reuptake Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Amines
ERG1 Potassium Channel
Ether-A-Go-Go Potassium Channels
KCNH2 protein, human
Neurotransmitter Uptake Inhibitors
Serotonin Uptake Inhibitors
Norepinephrine