A new class of diamine-based human histamine H3 receptor antagonists: 4-(aminoalkoxy)benzylamines

J Med Chem. 2003 Aug 28;46(18):3938-44. doi: 10.1021/jm030185v.

Abstract

4-(Aminoalkoxy)benzylamines were prepared and screened for in vitro activity at the human histamine H(3) receptor. Some members of this series exhibited subnanomolar binding affinities. Analogues in which one nitrogen atom was replaced with a methine group showed greatly reduced binding affinities. Six members of this series were found to be antagonists in a cell-based model of human histamine H(3) receptor activation. One member of this series, 1-[4-(3-piperidin-1-ylpropoxy)benzyl]piperidine (7b), was found to be a selective and potent human H(3) receptor antagonist.

MeSH terms

  • Animals
  • Benzylamines / chemical synthesis*
  • Benzylamines / metabolism
  • Benzylamines / pharmacology
  • Caco-2 Cells
  • Cell Line
  • Cerebral Cortex / metabolism
  • Cyclic AMP / biosynthesis
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / metabolism
  • Histamine Antagonists / pharmacology
  • Humans
  • In Vitro Techniques
  • Permeability
  • Piperidines / chemical synthesis*
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Rats
  • Receptors, Histamine H3 / drug effects*
  • Receptors, Histamine H3 / metabolism
  • Structure-Activity Relationship

Substances

  • 1-(4-(3-piperidin-1-ylpropoxy)benzyl)piperidine
  • Benzylamines
  • Histamine Antagonists
  • Piperidines
  • Receptors, Histamine H3
  • Cyclic AMP