Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives.
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.
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
Sorba
Giovanni
G
Fruttero
Roberta
R
Gasco
Alberto
A
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*
D006633:Histamine Antagonists; D007093:Imidazoles; D009573:Nitrites; D010069:Oxadiazoles; D010091:Oximes; D018100:Receptors, Histamine H3; C010166:furoxans; C413352:imoproxifan; D009569:Nitric Oxide