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

Article abstract of DOI:10.1016/j.bmcl.2010.03.082

A set of chiral imidazolylpropylguanidines and 2-aminothiazolylpropylguanidines bearing N^G-3-phenyl- or N^G-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.