Non-imidazole histamine NO-donor H3-antagonists.
Recently a series of H3-antagonists related to Imoproxifan was realised (I); in these products the oxime substructure of the lead was constrained in NO-donor furoxan systems and in the corresponding furazan derivatives. In this paper, a new series of compounds derived from I by substituting the imidazole ring with the ethoxycarbonylpiperazino moiety present in the non-imidazole H3-ligand A-923 is described. For all the products synthesis and preliminary pharmacological characterisation, as well as their hydrophilic-lipophilic balance, are reported. The imidazole ring replacement generally results in a decreased H3-antagonist activity with respect to the analogues of series I and, in some cases, induces relaxing effects on the electrically contracted guinea-pig ileum, probably due to increased affinity for other receptor systems.
Tosco
Paolo
P
Dipartimento di Scienza e Tecnologia del Farmaco, Via P. Giuria 9, I-10125 Torino, Italy.
Bertinaria
Massimo
M
Di Stilo
Antonella
A
Cena
Clara
C
Fruttero
Roberta
R
Gasco
Alberto
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D018100:Receptors, Histamine H3 / Q000502:physiology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D018100:Receptors, Histamine H3; C010166:furoxans; C069357:alpha-methylhistamine; D011899:Ranitidine; D011738:Pyrilamine