Synthesis and activity of a new class of dual acting norepinephrine and serotonin reuptake inhibitors: 3-(1 H-indol-1-yl)-3-arylpropan-1-amines

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 24; pp. 8455 - 8466
• Main Authors: Mahaney, Paige E., Vu, An T., McComas, Casey C., Zhang, Puwen, Nogle, Lisa M., Watts, William L., Sarkahian, Ani, Leventhal, Liza, Sullivan, Nicole R., Uveges, Albert J., Trybulski, Eugene J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.12.2006; Elsevier Science
• Subjects: Adrenergic Uptake Inhibitors - chemical synthesis; Adrenergic Uptake Inhibitors - pharmacology; Aryloxypropanamines; Biogenic Amines - chemical synthesis; Biogenic Amines - pharmacology; Biological and medical sciences; Cell Line, Tumor - drug effects; Choriocarcinoma - drug therapy; Choriocarcinoma - pathology; Dopamine Plasma Membrane Transport Proteins - metabolism; Humans; Indoles - chemical synthesis; Indoles - pharmacology; Medical sciences; Miscellaneous; Monoamine reuptake inhibitors; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Norepinephrine - antagonists & inhibitors; Norepinephrine reuptake inhibitors; Pharmacology. Drug treatments; Placenta - drug effects; Placenta - metabolism; Propylamines - chemical synthesis; Propylamines - pharmacology; Serotonin - chemistry; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin reuptake inhibitors; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - pharmacology; Structure-Activity Relationship; Norepinephrine reuptake inhibitors; Serotonin reuptake inhibitors; Monoamine reuptake inhibitors; Aryloxypropanamines; Endocrinopathy; Diseases of the osteoarticular system; Fibromyalgia; Selectivity; Reuptake inhibitor; Peripheral neuropathy; Pain; Peripheral nerve disease; Chemical synthesis; Nervous system diseases; Serotonin; Diabetes mellitus; Patient; Catecholamine; Biological activity; Striated muscle disease; Chronic; Biogenic amine; Neurotransmitter; Norepinephrine; Indole derivatives
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.08.039

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-(1 H-indol-1-yl)-3-arylpropan-1-amines.