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

Kumiko Takeuchi; Todd J Kohn; Nicholas A Honigschmidt; Vincent P Rocco; Patrick G Spinazze; Steven T Atkinson; Larry W Hertel; David L Nelson; D Bradley Wainscott; Laura J Ahmad; Janice Shaw; Penny G Threlkeld; David T Wong

doi:10.1016/j.bmcl.2003.09.002

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

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3939-42. doi: 10.1016/j.bmcl.2003.09.002.

Authors

Kumiko Takeuchi¹, Todd J Kohn, Nicholas A Honigschmidt, Vincent P Rocco, Patrick G Spinazze, Steven T Atkinson, Larry W Hertel, David L Nelson, D Bradley Wainscott, Laura J Ahmad, Janice Shaw, Penny G Threlkeld, David T Wong

Affiliation

¹ Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA. ktak@lilly.com

PMID: 14592479
DOI: 10.1016/j.bmcl.2003.09.002

Abstract

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.

MeSH terms

Antidepressive Agents / chemical synthesis*
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Indicators and Reagents
Molecular Conformation
Molecular Structure
Paroxetine / pharmacology
Piperidines / chemical synthesis*
Piperidines / pharmacology
Propanols / chemical synthesis*
Propanols / pharmacology
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Serotonin 5-HT1 Receptor Antagonists*
Structure-Activity Relationship

Substances

Antidepressive Agents
Indicators and Reagents
Piperidines
Propanols
Serotonin 5-HT1 Receptor Antagonists
Serotonin Uptake Inhibitors
Guanosine 5'-O-(3-Thiotriphosphate)
Paroxetine