1-(2-Phenoxyphenyl)methanamines: SAR for dual serotonin/noradrenaline reuptake inhibition, metabolic stability and hERG affinity.
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.
Whitlock
Gavin A
GA
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. gavin.whitlock@pfizer.com
Blagg
Julian
J
Fish
Paul V
PV
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008968:Molecular Conformation; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000588:Amines; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; C000606913:KCNH2 protein, human