3-(4-Piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles as bioavailable h5-HT2A antagonists

Bioorg Med Chem Lett. 2000 Dec 18;10(24):2701-3. doi: 10.1016/s0960-894x(00)00559-x.

Abstract

A series of 3-(4-piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles have been prepared and evaluated as ligands for the h5-HT2A receptor. 3-(8-Phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indole is a high-affinity (1.2nM), selective (>800 fold over h5-HT2C and hD2 receptors) antagonist at the h5-HT2A receptor with oral bioavailability in rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Binding, Competitive
  • Biological Availability
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Ligands
  • Piperidines / chemical synthesis
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Rats
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacokinetics
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • Ligands
  • Piperidines
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Serotonin Antagonists