Chiral N super(G)-acylated hetarylpropylguanidine-type histamine H sub(2) receptor agonists do not show significant stereoselectivity

A set of chiral imidazolylpropylguanidines and 2-aminothiazolylpropylguanidines bearing N super(G)-3-phenyl- or N super(G)-3-cyclohexylbutanoyl residues was synthesized and investigated for histamine H sub(2) receptor (H sub(2)R) agonism (guinea pig (gp) right atrium, GTPase assay on recombinant gp and human (h)H sub(2)R) and for hH sub(2)R selectivity compared to hH sub(1)R, hH sub(3)R and hH sub(4)R. 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 H sub(2)R agonists.