Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5251-6. doi: 10.1016/j.bmcl.2004.08.035.

Abstract

We describe the structure-activity relationships for a series of ligands structurally related to the recently identified (5-chloro-1H-indol-2-yl)-(4-methyl-piperazin-1-yl)-methanone (1) as histamine H(4) receptor (H(4)R) antagonists. Furthermore, we identified related benzimidazoles as novel lead compounds for the H(4)R. The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H(3) and H(4) receptors and exhibit pK(i) values up to 7.5 at the human H(4)R.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Binding, Competitive
  • Cell Line
  • Histamine H1 Antagonists / chemical synthesis*
  • Histamine H1 Antagonists / chemistry
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Ligands
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • HRH4 protein, human
  • Histamine H1 Antagonists
  • Indoles
  • Ligands
  • Piperazines
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4