Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626

Bioorg Med Chem. 2010 Jul 15;18(14):5291-300. doi: 10.1016/j.bmc.2010.05.052. Epub 2010 May 24.

Abstract

A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D2 versus D3 receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D2 binding affinity and the D2 versus D3 selectivity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Cell Line
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / chemistry*
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology
  • Protein Binding
  • Receptors, Dopamine D2 / metabolism*
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • 7-azaindole dimer
  • Benzofurans
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Indoles
  • Receptors, Dopamine D2
  • Thiophenes
  • benzothiophene
  • Adenylyl Cyclases
  • benzofuran