I2-Imidazoline Binding Site Affinity of a Structurally Different Type of Ligands

Abstract

Two families of compounds with affinity towards the I2 imidazoline binding sites are reported. The first is a family of compounds structurally related to agmatine with two guanidine or 2-aminoimidazoline groups at each end of an aliphatic chain of six, eight, nine or 12 methylene groups. Second, and following the model of clonidine, we propose another family of compounds also with two guanidine or 2-aminoimidazoline groups at each end of a chain consisting of two phenyl rings connected by groups such as CH2, CO, NH and SO2. The affinity of the compounds towards the I2 imidazoline binding sites was then evaluated in human brain tissues. In order to determine their pharmacological selectivity versus α2-adrenoceptors, the affinity for these receptors was also evaluated for the compounds with the highest affinities at I2 imidazoline binding sites. The results obtained show that many of the compounds exhibit a considerable affinity towards the I2 imidazoline binding sites. The aliphatic derivatives, in particular, present a very interesting selectivity for the I2 imidazoline binding sites versus the α2 adrenoceptors. To better understand these findings, mono-guanidinium analogues of the aliphatic derivatives were synthesised and tested showing poor affinity for I2 imidazoline binding sites. The importance of these results lies in the novelty of the chemical structures studied (dicationic aliphatic compounds particularly) because they are significantly different to those of the I2 imidazoline binding site ligands reported to date.