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

…, A Spickenreither, I Brunskole, M Lopuch…

Index: Birnkammer, Tobias; Spickenreither, Anja; Brunskole, Irena; Lopuch, Miroslaw; Kagermeier, Nicole; Bernhardt, Guenther; Dove, Stefan; Seifert, Roland; Elz, Sigurd; Buschauer, Armin Journal of Medicinal Chemistry, 2012 , vol. 55, # 3 p. 1147 - 1160

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Citation Number: 26

Abstract

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 human (h) H2R-GsαS fusion proteins ...