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The bivalent ligand approach leads to highly potent and selective acylguanidine-type histamine H2 receptor agonists

Birnkammer, Tobias ; Spickenreither, Anja ; Brunskole, Irena ; Lopuch, Miroslaw ; Kagermeier, Nicole ; Bernhardt, Günther ; Dove, Stefan ; Seifert, Roland ; Elz, Sigurd ; Buschauer, Armin


Bivalent histamine H2 receptor (H2R) agonists were synthesized by connecting pharmacophoric 3-(2-amino-4-methylthiazol-5-yl)-, 3-(2-aminothiazol-5-yl)-, 3-(imidazol-4-yl)- or 3-(1,2,4-triazol-5-yl)-propylguanidine moieties by NG-acylation with alkanedioic acids of various chain lengths. The compounds were investigated for H2R agonism in GTPase and [35S]GTPγS binding assays at guinea pig (gp) and ...


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