Advances toward new antidepressants beyond SSRIS: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 4

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 10; pp. 2653 - 2656
• Main Authors: ROCCO, Vincent P, SPINAZZE, Patrick G, TAKEUCHI, Kumiko, KOHN, Todd J, HONIGSCHMIDT, Nicholas A, NELSON, David L, WAINSCOTT, D. Bradley, AHMAD, Laura J, SHAW, Janice, THRELKELD, Penny G, WONG, David T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 17-05-2004
• Subjects: Antidepressive Agents, Second-Generation - chemical synthesis; Antidepressive Agents, Second-Generation - pharmacology; Biological and medical sciences; Heterocyclic Compounds, 4 or More Rings - chemical synthesis; Heterocyclic Compounds, 4 or More Rings - pharmacology; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Propanols - chemical synthesis; Propanols - pharmacology; Protein Binding; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Serotonin 5-HT1 Receptor Antagonists; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; Stereoisomerism; Structure-Activity Relationship; Serotonin; Nitrogen heterocycle; Psychotropic; Oxygen heterocycle; Reuptake inhibitor; In vitro; 5-HT1A Serotonine receptor; Structure activity relation; Piperidine derivatives; Antidepressant agent; Antagonist; Benzofuran derivatives; Secondary alcohol; Indole derivatives; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.02.088

A series of 1-(1H-indol-4-yloxy)-3-(4-arylpiperidinyl)propan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. The fused aryl ring moiety contributed to the robust dual activities irrespective of the regiochemistry associated with its connectivity to the piperidine central ring.