3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α2-adrenoceptor compared to the imidazoline I1 receptor

Abstract A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective α 2 -adrenoceptor ligand. Parent compound 4a and its 4-chloro ( 4c ) and 4-methyl ( 4d ) derivatives display α 2 -adrenoceptor affinity at nanomolar concentrations ( K i  = 39.4, 15.9 and 22.6 nM, respectively) and relatively high α 2 /I 1 selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at α 2A -adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01 mg/kg iv