[3-(1H-imidazol-4-yl)propyl]guanidines containing furoxan moyeties: a new class of H3-agonists endowed with NO-donor properties

Synthesis and pharmacological characterisation of a series of products obtained by coupling the H-3-antagonist SKF 91486 through appropriate spacers with the NO-donor 3-phenylfuroxan-4-yloxy and 3-benzenesulfonylfuroxan-4-yloxy moieties, as well as with the corresponding furazan substructures, devoid of NO-donating properties, are reported. All the products were tested for their H-3-antagonistic and H-2-agonistic properties on electrically-stimulated guinea-pig ileum segments and guinea-pig papillary muscle, respectively. The whole series of compounds displayed good H-3-antagonist behaviour and feeble partial H-2-agonist activity. Among furoxan derivatives, the benzenesulfonyl hybrid 28, a good NO-donor, triggered a dual NO-dependent muscle relaxation and H3-antagonistic effect on guinea-pig intestine