Pharmacophore Development and SAR Studies of Imidazoline Receptor Ligands

Relationship between biological responses and binding affinities at I1/I2/I3 imidazoline receptors of compounds with imidazoline, pyrroline or oxazoline moieties was studied by 2D-QSAR, 3D-QSAR and quantitative pharmacophore development approaches. Since the I1 imidazoline receptor is involved in central inhibition of sympathicus that produce hypotensive effect, the I2 receptor is allosteric modulator of monoamine oxidase B (MAO-B) and the I3 receptor regulates insulin secretion from pancreatic β-cells, design and synthesis of selective I1/I2/I3 imidazoline ligands are very important for the development of new effective therapeutic agents. New agonists and antagonists with high selectivity for I1/I2/I3 imidazoline receptor classes have been recently synthesized and examined. The present review will highlight the main chemical diversity and pharmacophore features of selective I1/I2/I3 imidazoline receptor ligands.