Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole

Article abstract of DOI:10.1021/jm00002a008

The influence of alkyl chain length variation on the histamine H₃ receptor activity of histamine homologs 1 was investigated.A series of 4(5)-(ω-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups.Besides the H₃ activity, the affinities of these compounds for the H₁ and H₂ receptors were determined.The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes.For the H₃ receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H₃ antagonist from this series of 4(5)-(ω-aminoalkyl)-1H-imidazoles 1, with a pA₂ value of 8.4 (on guinea pig jejunum).A specific antagonistic binding site for this compound is proposed.