Chiral NG-acylated hetarylpropylguanidine-type histamine H2 receptor agonists do not show significant stereoselectivity

A set of chiral imidazolylpropylguanidines and 2-aminothiazolylpropylguanidines bearing NG-3-phenyl- or NG-3-cyclohexylbutanoyl residues was synthesized and investigated for histamine H2 receptor (H2R) agonism (guinea pig (gp) right atrium, GTPase assay on recombinant gp and human (h)H2R) and for hH2R selectivity compared to hH1R, hH3R and hH4R. In contrast to previous studies on arpromidine derivatives, the present investigation of acylguanidine-type compounds revealed only very low eudismic ratios (1.1–3.2), indicating the stereochemistry of the acyl moiety to play only a minor role in this series of H2R agonists.

The synthesis and pharmacological characterisation of the enantiomers of the title compounds on recombinant histamine receptors (gpH2R and hH2R, hH1R, hH3R, hH4R) and on the isolated guinea pig atrium is described.Figure optionsDownload as PowerPoint slide