title: Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives.
abstract: Synthesis and pharmacological characterisation of a series of compounds in which the oxime substructure present in imoproxifan was constrained in the pentatomic NO-donor furoxan ring, as well as their structurally related furazan analogues devoid of NO-donating properties, are described. The whole series of products displayed reversible histamine H3-antagonistic activity on guinea-pig ileum. 4-(4-(3-(1H-Imidazol-4-yl)propoxy)phenyl)furoxan-3-carbonitrile 16 was also able to induce partial relaxation when added to the bath after electrical contraction of the guinea-pig ileum during the study of its H3-antagonistic properties. This phenomenon seems to be dependent on NO-mediated sGC activation. The lipophilic-hydrophilic balance of all the products was investigated.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Via P. Giuria 9, I-10125 Torino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tosco
authors.forename: Massimo
authors.initials: M
authors.lastname: Bertinaria
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Stilo
authors.forename: Clara
authors.initials: C
authors.lastname: Cena
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorba
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D009573:Nitrites; D010069:Oxadiazoles; D010091:Oximes; D018100:Receptors, Histamine H3; C010166:furoxans; C413352:imoproxifan; D009569:Nitric Oxide