N-Benzyl-N-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amines as selective dual serotonin/noradrenaline reuptake inhibitors.
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.
Fish
Paul V
PV
Sandwich Chemistry Department, Pfizer Global Research and Development, Sandwich Labs, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Fray
M Jonathan
MJ
Stobie
Alan
A
Wakenhut
Florian
F
Whitlock
Gavin A
GA
D000588:Amines / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D015195:Drug Design; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D008968:Molecular Conformation; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000588:Amines; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; D008024:Ligands; D009638:Norepinephrine; D011759:Pyrrolidines; D017367:Selective Serotonin Reuptake Inhibitors; C496884:KCNH1 protein, human