Histamine analogues: imidazolylalkylguanidines, synthesis and in vitro pharmacology

Structure-Activity Relationships of Histamine H2 Receptor Ligands+

“…This partial structure shows a lower degree of stereoselectivity than the imidazolylpropyl portion [44], which is conferring efficacy and may be varied or replaced over a wide range, resulting in H 2 R agonists with similar or even higher potency than the parent compound. The structural analogues of impromidine described in the literature include, for example, chiral compounds with branched cimetidine-like or homohistamine partial structures [44,45] or substances characterised by other substructures from H 2 R antagonists like thiazoles and furans derived from tiotidine, nizatidine and ranitidine [46,47]. Completely different structures replacing the 5-methylimidazole group are present in the case of hybrid molecules combining the imidazolylpropylguanidine moiety with, for example, arylalkyl [48][49][50][51][52][53][54][55][56], diarylalkyl originating from H 1 R antagonists [57][58][59][60][61], dihydropyridine from calcium channel blockers [62,63] and benzoylimidazolone groups [64] from phosphodiesterase inhibitors (for reviews see [15,65,66]).…”