[3-(1H-imidazol-4-yl)propyl]guanidines containing furoxan moieties: a new class of H3-antagonists 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 H(3)-antagonistic effect on guinea-pig intestine.
Bertinaria
Massimo
M
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, I-10125 Turin, Italy.
Stilo
Antonella Di
AD
Tosco
Paolo
P
Sorba
Giovanni
G
Poli
Enzo
E
Pozzoli
Cristina
C
Coruzzi
Gabriella
G
Fruttero
Roberta
R
Gasco
Alberto
A
D000818:Animals; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000187:drug effects*
D006146:Guanidines; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D007202:Indicators and Reagents; D020030:Nitric Oxide Donors; D009573:Nitrites; D018100:Receptors, Histamine H3