Synthesis and histamine H2-receptor activity of heterocyclic impromidine analogues

Pharmazie. 1992 Feb;47(2):86-91.


Analogues of the H2-agonist impromidine with unsubstituted or substituted aromatic or non-aromatic heterocycles instead of the 5-methylimidazole group were prepared via the benzoylguanidine method and tested for H2-agonistic and H1-antagonistic activity in the guinea-pig isolated right atrium and ileum, respectively. Compounds with unsubstituted 2- or 3-pyridyl, 2-pyrazinyl, or 5-pyrimidyl thioether portion proved to be about equipotent in the atrium (about 2-4x histamine). Highest potency was found in the 5-chloro-3-pyridylthioethylguanidine 8h, that is about 20 times more potent as an H2-agonist than histamine, corresponding to about 8 times the activity of the unsubstituted parent compound 8g. It is demonstrated by the piperidinyl- and morpholinylalkyl guanidines 8m-o that an aromatic ring is not required in the affinity-conferring moiety of H2-agonists (8n: 1.3x histamine). Replacement of the (5-methylimidazol-4-yl)methylthio group in the H2-antagonist cimetidine by halogenated pyridyl, pyrazinyl and pyrimidinyl thioethers resulted in compounds inactive as H2-antagonists, giving further evidence for differences in the structural requirements of the affinity-conferring portions of H2-agonists and antagonists and their mode of interaction with the receptor protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Guanidines / chemical synthesis*
  • Guinea Pigs
  • Heart Atria / drug effects
  • Histamine / pharmacology
  • Histamine H1 Antagonists / pharmacology
  • Ileum / drug effects
  • Imidazoles / chemical synthesis*
  • Impromidine
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Receptors, Histamine H2 / drug effects*


  • Guanidines
  • Histamine H1 Antagonists
  • Imidazoles
  • Receptors, Histamine H2
  • Histamine
  • Impromidine