Methylation of imidazoline related compounds leads to loss of α2-adrenoceptor affinity. Synthesis and biological evaluation of selective I1 imidazoline receptor ligands

Methylated analogues of imidazoline related compounds (IRC) were prepared; their abilities to bind I1 imidazoline receptors (I1Rs), I2 imidazoline binding sites (I2BS) and α2-adrenoceptor subtypes (α2ARs) were assessed. Methylation of the heterocyclic moiety of IRC resulted in a significant loss of α2AR affinity. Amongst the selective ligands obtained, LNP 630 (4) constitutes the first highly selective I1R agent showing hypotensive activity after intravenous administration.