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

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 22; pp. 3939 - 3942
• Main Authors: TAKEUCHI, Kumiko, KOHN, Todd J, SHAW, Janice, THRELKELD, Penny G, WONG, David T, HONIGSCHMIDT, Nicholas A, ROCCO, Vincent P, SPINAZZE, Patrick G, ATKINSON, Steven T, HERTEL, Larry W, NELSON, David L, WAINSCOTT, D. Bradley, AHMAD, Laura J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 17-11-2003
• Subjects: Antidepressive Agents - chemical synthesis; Biological and medical sciences; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Indicators and Reagents; Medical sciences; Molecular Conformation; Molecular Structure; Neuropharmacology; Paroxetine - pharmacology; Pharmacology. Drug treatments; Piperidines - chemical synthesis; Piperidines - pharmacology; Propanols - chemical synthesis; Propanols - pharmacology; 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; Structure-Activity Relationship; Aminoalcohol; Serotonin; Nitrogen heterocycle; Psychotropic; Aminoether; Oxygen heterocycle; Reuptake inhibitor; In vitro; Sulfur heterocycle; 5-HT1A Serotonine receptor; Structure activity relation; Membrane transport; Piperidine derivatives; Bicyclic compound; Affinity; Antidepressant agent; Aromatic compound; Antagonist; Benzofuran derivatives; Inhibition; Indole derivatives; Chemical synthesis; Carrier protein
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.09.002

A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. Modification of potential metabolic sites of 1-(1H-indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols further improved the in vitro binding affinities and functional antagonism.