Imidazoline-modified benzylimidazolines as h5-HT(1D/1B) serotonergic ligands

Bioorg Med Chem. 2001 Mar;9(3):613-9. doi: 10.1016/s0968-0896(00)00275-3.

Abstract

Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h5-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-HT(1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced (i.e., > 100-fold) h5-HT1D versus hS-HT1B selectivity.

MeSH terms

  • Benzyl Compounds / chemical synthesis
  • Benzyl Compounds / metabolism
  • Benzyl Compounds / pharmacology*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / metabolism
  • Imidazoles / pharmacology*
  • Ligands
  • Migraine Disorders / drug therapy
  • Protein Binding
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin / metabolism*
  • Serotonin Agents / chemical synthesis*
  • Serotonin Agents / metabolism
  • Serotonin Agents / pharmacology
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Benzyl Compounds
  • HTR1B protein, human
  • Imidazoles
  • Ligands
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin Receptor Agonists