H3 receptor ligands: new imidazole H3-antagonists endowed with NO-donor properties.
Synthesis and pharmacological properties of a group of compounds obtained by coupling the H(3)-antagonist SKF 91486 with the NO-donor 3-phenylfuroxan-4-yloxy and 3-benzenesulfonylfuroxan-4-yloxy moieties, as well as with the corresponding furazan analogues, devoid of NO-donating properties, are reported. All the products were tested for their H(3)-antagonistic and H(2)-agonistic properties on electrically-simulated guinea-pig ileum segments and guinea-pig papillary muscle, respectively. All the synthesised compounds displayed good H(3)-antagonistic properties (pA(2) range 7.02-8.49) while behaving only as weak partial H(2)-agonists. Derivative 28, the best NO-donor of the series, was able to trigger a dual NO-dependent muscle relaxation and H(3)-antagonistic effect on guinea-pig illeum.
Bertinaria
Massimo
M
Dipartimento di Scienza e Tecnologia del Farmaco, Via P Giuria, 9-10125 Turin, Italy. massimo.bertinaria@unito.it
D000818:Animals; D006633:Histamine Antagonists / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D006633:Histamine Antagonists; D008024:Ligands; D020030:Nitric Oxide Donors; D018100:Receptors, Histamine H3