Synthesis and α-Adrenergic Binding Ligand Affinities of 2-Iminoimidazolidine Derivatives

In order to obtain possible veinotonic drugs acting through α2 receptor activation, we prepared clonidine analogues in which the 2-imino-imidazolidine was attached to various aliphatic or aromatic heterocycles. Among them, the two benzopyranic derivatives 16 and 22 exhibited interesting affinities (19 and 95 nM respectively on [3H]rauwolscine binding, compared to 35 nM for clonidine). Their affinity for α1 receptors was found to be much lower : 7570 and 5030 nM for 16 and 22 respectively, suggesting 16 to be 400 times more selective for α2 than for α1-adrenoceptors.