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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Electric Stimulation / methods
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Guinea Pigs
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Histamine Agonists / pharmacology
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Histamine Antagonists / chemical synthesis
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Histamine Antagonists / pharmacology*
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Ileum / drug effects
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Ileum / physiology
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology
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In Vitro Techniques
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Male
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Methylhistamines / pharmacology
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Muscle Relaxation / drug effects
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Muscle Relaxation / physiology
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Nitric Oxide Donors / chemical synthesis
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Nitric Oxide Donors / pharmacology*
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Oxadiazoles / pharmacology
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Pyrilamine / pharmacology
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Quinoxalines / pharmacology
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Ranitidine / pharmacology
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Receptors, Histamine H3 / physiology*
Substances
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1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
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Histamine Agonists
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Histamine Antagonists
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Imidazoles
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Methylhistamines
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Nitric Oxide Donors
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Oxadiazoles
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Quinoxalines
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Receptors, Histamine H3
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furoxans
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alpha-methylhistamine
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Ranitidine
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Pyrilamine