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

Bioorg Med Chem Lett. 2010 May 15;20(10):3173-6. doi: 10.1016/j.bmcl.2010.03.082. Epub 2010 Mar 27.

Abstract

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 H(2) receptor (H(2)R) agonism (guinea pig (gp) right atrium, GTPase assay on recombinant gp and human (h)H(2)R) and for hH(2)R selectivity compared to hH(1)R, hH(3)R and hH(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(2)R agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Guanidines / chemical synthesis
  • Guanidines / chemistry
  • Guanidines / pharmacology
  • Guinea Pigs
  • Histamine Agonists / chemical synthesis
  • Histamine Agonists / chemistry*
  • Histamine Agonists / pharmacology
  • Humans
  • Receptors, Histamine H2 / chemistry*
  • Receptors, Histamine H2 / genetics
  • Receptors, Histamine H2 / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Stereoisomerism

Substances

  • Guanidines
  • Histamine Agonists
  • Receptors, Histamine H2
  • Recombinant Proteins
  • propylguanidine