Synthesis and activity of a new class of dual acting norepinephrine and serotonin reuptake inhibitors: 3-(1H-indol-1-yl)-3-arylpropan-1-amines.
Compounds with a combination of norepinephrine and serotonin reuptake inhibition have been approved in the US and Europe for a number of indications, including major depressive disorder and pain disorders such as diabetic neuropathy and fibromyalgia. Efforts to design selective norepinephrine reuptake inhibitors based on SAR from the aryloxypropanamine series of monoamine reuptake inhibitors have led to the identification of a potent new class of dual acting norepinephrine and serotonin reuptake inhibitors, namely the 3-(1H-indol-1-yl)-3-arylpropan-1-amines.
Mahaney
Paige E
PE
Chemical and Screening Sciences, Discovery Medicinal Chemistry, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. mahanep@wyeth.com
Vu
An T
AT
McComas
Casey C
CC
Zhang
Puwen
P
Nogle
Lisa M
LM
Watts
William L
WL
Sarkahian
Ani
A
Leventhal
Liza
L
Sullivan
Nicole R
NR
Uveges
Albert J
AJ
Trybulski
Eugene J
EJ
D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D001679:Biogenic Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002822:Choriocarcinoma / Q000188:drug therapy / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011437:Propylamines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012701:Serotonin / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018759:Adrenergic Uptake Inhibitors; D001679:Biogenic Amines; D050483:Dopamine Plasma Membrane Transport Proteins; D007211:Indoles; D009638:Norepinephrine; D011437:Propylamines; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human