Methylation of imidazoline related compounds leads to loss of α₂-adrenoceptor affinity. Synthesis and biological evaluation of selective I₁ imidazoline receptor ligands

Bioorg Med Chem. 2012 Aug 1;20(15):4710-5. doi: 10.1016/j.bmc.2012.06.008. Epub 2012 Jun 9.

Abstract

Methylated analogues of imidazoline related compounds (IRC) were prepared; their abilities to bind I(1) imidazoline receptors (I(1)Rs), I(2) imidazoline binding sites (I(2)BS) and α(2)-adrenoceptor subtypes (α(2)ARs) were assessed. Methylation of the heterocyclic moiety of IRC resulted in a significant loss of α(2)AR affinity. Amongst the selective ligands obtained, LNP 630 (4) constitutes the first highly selective I(1)R agent showing hypotensive activity after intravenous administration.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • CHO Cells
  • Cricetinae
  • Humans
  • Imidazoline Receptors / chemistry*
  • Imidazoline Receptors / metabolism
  • Imidazolines / administration & dosage
  • Imidazolines / chemistry*
  • Imidazolines / pharmacology*
  • Injections, Intravenous
  • Ligands
  • Male
  • Methylation
  • Molecular Structure
  • PC12 Cells
  • Rats
  • Rats, Inbred SHR
  • Receptors, Adrenergic, alpha-2 / chemistry*
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Structure-Activity Relationship

Substances

  • Imidazoline Receptors
  • Imidazolines
  • Ligands
  • Receptors, Adrenergic, alpha-2
  • imidazoline I1 receptors
  • imidazoline receptor 2