53179-07-0

Basic information

• Product Name: Nisoxetine
• Synonyms: Nisoxetine;Compound 89218;[3-(2-Methoxy-phenoxy)-3-phenyl-propyl]-methyl-amine
• CAS NO: 53179-07-0
• Molecular Formula: C₁₇H₂₁NO₂
• Molecular Weight: 271.35
• Mol File: 53179-07-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 404.8°Cat760mmHg
• Flash Point: 170.6°C
• Appearance: /
• Density: 1.054g/cm³
• Vapor Pressure: 9.2E-07mmHg at 25°C
• Refractive Index: 1.547
• PKA: 10.16±0.10(Predicted)
• CAS DataBase Reference: Nisoxetine(CAS DataBase Reference)
• NIST Chemistry Reference: Nisoxetine(53179-07-0)
• EPA Substance Registry System: Nisoxetine(53179-07-0)

Safety Data

• Hazardous Substances Data: 53179-07-0(Hazardous Substances Data)

Usage

Uses

Antidepressant.

General Description

Nisoxetine is a SNERI and is an antidepressant. Most activityresides in the β-isomer.

Clinical Use

Nisoxetine was the initial phenoxyphenylpropylamine synthesized in the Lilly research laboratories during the early 1970s from the rearrangement of an oxygen atom in diphenyhydramine, a diphenylmethoxyethylamine, to a phenoxyphenylpropylamine. Nisoxetine was discovered to be a potent and very selective SNRI, with little affinity for other receptors. It underwent clinical studies as an alternative to Lilly's best-selling antidepressant, nortriptyline, but without the adverse effects associated with the tricyclic secondary amines. It was never marketed, however, because of a greater interest in developing its 4-trifluoromethyl analogue, fluoxetine, an SSRI.

InChI:InChI=1/C17H21NO2/c1-18-13-12-15(14-8-4-3-5-9-14)20-17-11-7-6-10-16(17)19-2/h3-11,15,18H,12-13H2,1-2H3

Upstream product

• 21763-00-8 1-bromo-3-chloro-1-phenylpropane 
• 104-52-9 phenylpropyl chloride 
• 57226-60-5 3-chloro-1-(o-methoxyphenoxy)propylbenzene 
• 74-89-5 methylamine 

Relevant articles and documents

Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac)

Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model comparedwith the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity. Copyright

Aryloxyphenylpropylamines in treating depression

3-Aryloxy-3-phenylpropylamines and acid additions salts thereof, useful as psychotropic agents, particularly as anti-depressants.