The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine

The affinity of the pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine for a panel of 5-HT receptors has been determined. The affinity of the analogs is compared and contrasted with that of the parent compounds. The trifluoromethyl group of fluoxetine 1 and fenfluramine and...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2007-11, Vol.15 (21), p.6659-6666
Main Authors: Welch, John T., Lim, Dong Sung
Format: Article
Language:English
Subjects:
5-HT receptors
5-Hydroxytryptamine
Animals
Biological and medical sciences
Fenfluramine
Fenfluramine - analogs & derivatives
Fenfluramine - chemical synthesis
Fenfluramine - chemistry
Fenfluramine - pharmacology
Fluoxetine
Fluoxetine - chemistry
Fluoxetine - pharmacology
Humans
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Norfenfluramine
Norfenfluramine - chemistry
Norfenfluramine - pharmacology
Pentafluorosulfanyl group
Pharmacology. Drug treatments
Receptors, Serotonin - drug effects
Serotonin
Serotonin Uptake Inhibitors - chemical synthesis
Serotonin Uptake Inhibitors - chemistry
Serotonin Uptake Inhibitors - pharmacology
Serotoninergic system
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Summary:The affinity of the pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine for a panel of 5-HT receptors has been determined. The affinity of the analogs is compared and contrasted with that of the parent compounds. The trifluoromethyl group of fluoxetine 1 and fenfluramine and norfenfluramine, 2 and 3, was substituted by the pentafluorosulfanyl group. On examination of the efficacy of the pentafluorosulfanyl containing compounds as inhibitors of 5-hydroxytryptamine receptors, it was found that substitution could lead to enhanced selectivity and in the case of the pentafluorosulfanyl analog of fenfluramine, 18, it significantly enhanced potency against the 5-HT 2b, 5-HT 2c, and 5-HT 6 receptors.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2007.08.012