Identification of 2-arylbenzimidazoles as potent human histamine H4 receptor ligands

Bioorg Med Chem Lett. 2006 Dec 1;16(23):6043-8. doi: 10.1016/j.bmcl.2006.08.117. Epub 2006 Sep 20.

Abstract

A series of 2-arylbenzimidazoles was synthesized and found to bind with high affinity to the human histamine H(4) receptor. Structure-activity relationships were investigated through library preparation and evaluation as well as traditional medicinal chemistry approaches, leading to the discovery of compounds with single-digit nanomolar affinity for the H(4) receptor.

MeSH terms

  • Aldehydes / chemistry
  • Amines / chemistry
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / metabolism*
  • Catalysis
  • Computer Simulation
  • Histamine / metabolism
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Histamine / chemistry
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H4
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Amines
  • Benzimidazoles
  • HRH4 protein, human
  • Ligands
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Histamine