Discovery of novel lead in the group of N-substituted piperazine ether derivatives with potential histamine H3 receptor activity

Med Chem. 2014;10(6):588-99. doi: 10.2174/15734064113096660050.

Abstract

The search for novel lead from the group of various substituted N-piperazine ether derivatives was performed. Acyl- and pyridylpiperazine ethyl/propyl ethers were obtained via three different synthetic pathways. Affinity to histamine H3 receptor was established, as well as, for selected compounds, selectivity towards histamine H4R. Docking studies to the histamine H3R homology model strengthened the position of (4-(3-(4-(3-chlorobenzoyl)piperazin-1- yl)propoxy)phenyl)(cyclopropyl)methanone (compound 26) as a novel lead for further studies on histamine H3 receptor antagonist/inverse agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • CHO Cells
  • Cricetulus
  • Drug Discovery / methods*
  • Ethers
  • Histamine Agonists / chemical synthesis*
  • Histamine Agonists / chemistry
  • Histamine Agonists / pharmacology
  • Histamine H3 Antagonists / chemical synthesis*
  • Histamine H3 Antagonists / chemistry
  • Histamine H3 Antagonists / pharmacology
  • Ligands
  • Molecular Docking Simulation
  • Molecular Structure
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Histamine / chemistry
  • Receptors, Histamine / metabolism
  • Receptors, Histamine H3 / chemistry*
  • Receptors, Histamine H3 / genetics
  • Receptors, Histamine H4

Substances

  • 4-(3-(4-(3-chlorobenzoyl)piperazin-1-yl)propoxy)phenyl)(cyclopropyl)methanone
  • Ethers
  • HRH4 protein, human
  • Histamine Agonists
  • Histamine H3 Antagonists
  • Ligands
  • Piperazines
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H3
  • Receptors, Histamine H4