Non-imidazole histamine NO-donor H3-antagonists

Abstract

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.