[4-(Phenoxy)pyridin-3-yl]methylamines: a new class of selective noradrenaline reuptake inhibitors.
[4-(Phenoxy)pyridine-3-yl]methylamines are disclosed as a new series of selective noradrenaline reuptake inhibitors (NRI). Structure-activity relationships established that potent NRI activity could be achieved by appropriate substitution at the 2-position of the phenoxy ring. Compound 31 demonstrated potent NRI activity combined with good selectivity over serotonin and dopamine reuptake and no significant off-target pharmacology.
Fish
Paul V
PV
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. paul.fish@pfizer.com
Ryckmans
Thomas
T
Stobie
Alan
A
Wakenhut
Florian
F
D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D065607:Cytochrome P-450 Enzyme Inhibitors; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008744:Methylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D017551:Microdialysis; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017397:Prefrontal Cortex / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018759:Adrenergic Uptake Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; D008744:Methylamines; D009638:Norepinephrine; D011725:Pyridines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C496884:KCNH1 protein, human