Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective ligands

Bioorg Med Chem. 2001 Mar;9(3):585-92. doi: 10.1016/s0968-0896(00)00280-7.

Abstract

Several series of 2-aryl or heterocyclic-imidazoline compounds have been prepared and evaluated in vitro as imidazoline sites (I1 and I2) and alpha-adrenergic (alpha1 and alpha2) receptor ligands. Their pKi values indicate that linkage of the imidazoline moiety at the 2-position with an aromatic substituent dramatically decreases alpha-adrenergic affinity. I1 sites are more accessible by phenyl imidazolines substituted by a methyl or a methoxy group at the ortho or meta position. Indeed, 2-(2'-methoxyphenyl)-imidazoline (17) is one of the best I1 ligands ever reported (pKi = 8.53 and I1/I2 > 3388). On the other hand, I2 selectivity increases in the presence of a methyl group in the para position. The original compound, 2-(3'-fluoro-4'-tolyl)-imidazoline (31) is a new potent ligand for the I2 sites with high selectivity (pKi = 8.53 and I2/I1 > 3388).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / ultrastructure
  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / metabolism
  • Binding Sites
  • Cattle
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cerebral Cortex / ultrastructure
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology*
  • Imidazoline Receptors
  • Kidney Cortex / ultrastructure
  • Ligands
  • Rabbits
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Receptors, Drug / metabolism*
  • Structure-Activity Relationship

Substances

  • Antihypertensive Agents
  • Imidazoles
  • Imidazoline Receptors
  • Ligands
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, Drug