Pharmacophore Development and SAR Studies of Imidazoline Receptor Ligands

Abstract

Relationship between biological responses and binding affinities at I-1/I-2/I-3 imidazoline receptors of compounds with imidazoline, pyrroline or oxazoline moieties was studied by 2D-QSAR, 3D-QSAR and quantitative pharmacophore development approaches. Since the I-1 imidazoline receptor is involved in central inhibition of sympathicus that produce hypotensive effect, the I-2 receptor is allosteric modulator of monoamine oxidase B (MAO-B) and the I-3 receptor regulates insulin secretion from pancreatic beta-cells, design and synthesis of selective I-1/I-2/I-3 imidazoline ligands are very important for the development of new effective therapeutic agents. New agonists and antagonists with high selectivity for I-1/I-2/I-3 imidazoline receptor classes have been recently synthesized and examined. The present review will highlight the main chemical diversity and pharmacophore features of selective I-1/I-2/I-3 imidazoline receptor ligands.