Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist

J Med Chem. 2004 May 6;47(10):2414-7. doi: 10.1021/jm049932u.

Abstract

In this study, the piperidine ring of immepip and its analogues was replaced by a rigid heterocyclic pyridine ring. Many compounds in the series exhibit high affinity and agonist activity at the human histamine H(3) receptor. Particularly, the 4-pyridinyl analogue of immepip (1c, immethridine) is identified as a novel potent and highly selective histamine H(3) receptor agonist (pK(i) = 9.07, pEC(50) = 9.74) with a 300-fold selectivity over the closely related H(4) receptor.

MeSH terms

  • Animals
  • Cell Line
  • Guinea Pigs
  • Histamine Agonists / chemical synthesis*
  • Histamine Agonists / chemistry
  • Histamine Agonists / pharmacology
  • Humans
  • Ileum / drug effects
  • Ileum / innervation
  • Ileum / physiology
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Myenteric Plexus / drug effects
  • Myenteric Plexus / physiology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Radioligand Assay
  • Receptors, Histamine H3 / drug effects*
  • Receptors, Histamine H3 / metabolism
  • Structure-Activity Relationship

Substances

  • Histamine Agonists
  • Imidazoles
  • Pyridines
  • Receptors, Histamine H3