Advances Toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT(1A) receptor antagonism/SSRI activities. Part 2

Bioorg Med Chem Lett. 2003 Jul 21;13(14):2393-7. doi: 10.1016/s0960-894x(03)00392-5.

Abstract

Potent 5-HT1A/SSRIs at low nanomolar and subnanomolar concentrations were identified in a series of 1-(1H-indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols. Incorporation of an alpha-Me group in the piperidine ring with its specific stereochemistry enhanced binding affinity at the 5-HT reuptake site and in vitro 5-HT(1A) antagonist functional activity.

Publication types

  • Comparative Study

MeSH terms

  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Indicators and Reagents
  • Paroxetine / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology*
  • Propanols / chemical synthesis*
  • Propanols / pharmacology*
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Indicators and Reagents
  • Piperidines
  • Propanols
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Paroxetine