Modulation of selective serotonin reuptake inhibitor and 5-HT1A antagonist activity in 8-aza-bicyclo[3.2.1]octane derivatives of 2,3-dihydro-1,4-benzodioxane

Bioorg Med Chem Lett. 2004 Jan 19;14(2):515-8. doi: 10.1016/j.bmcl.2003.10.024.

Abstract

2,3-Dihydro-1,4-benzodioxanes with aryl 8-aza-bicyclo[3.2.1]oct-3-ene attachments 2 produce compounds with potent 5-HT-T affinity, and weak 5-HT(1A) affinity and alpha(1) affinity. This compares with 2,3-dihydro-1,4-benzodioxanes containing 8-aza-bicyclo[3.2.1] octan-3-ol attachments 4 which possess potent 5-HT(1A) affinity, moderate to good selectivity over alpha(1) and little 5-HT-T affinity. A 3-benzothiophene analogue of 4 (30) was synthesized which possesses potent 5-HT(1A) affinity and especially good selectivity over both alpha(1) and 5-HT-T.

MeSH terms

  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds / pharmacology*
  • Dioxanes / metabolism
  • Dioxanes / pharmacology*
  • Humans
  • Octanes / metabolism
  • Octanes / pharmacology*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin 5-HT1 Receptor Antagonists*
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology*

Substances

  • Bridged Bicyclo Compounds
  • Dioxanes
  • Octanes
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A