Synthesis and SAR of aminoalkoxy-biaryl-4-carboxamides: novel and selective histamine H3 receptor antagonists

Bioorg Med Chem Lett. 2003 Apr 7;13(7):1325-8. doi: 10.1016/s0960-894x(03)00118-5.

Abstract

Novel 4'-[(NR1R2-1-yl)]-propoxy-biaryl-4-carboxamides were designed and synthesized. All compounds were tested for affinity at histamine H(3)receptors. Most compounds were highly potent and selective for human and rat H(3) receptors and selected examples such as A-349821 showed functional antagonism of H(3) receptors in vitro and in a mouse dipsogenia model.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Amines / chemical synthesis*
  • Amines / pharmacology*
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Dogs
  • Dose-Response Relationship, Drug
  • Drinking Behavior / drug effects
  • Haplorhini
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / pharmacology*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Radioligand Assay
  • Rats
  • Receptors, Biogenic Amine / drug effects
  • Receptors, Biogenic Amine / metabolism
  • Receptors, Histamine H3 / drug effects*
  • Structure-Activity Relationship

Substances

  • Amides
  • Amines
  • Histamine Antagonists
  • Receptors, Biogenic Amine
  • Receptors, Histamine H3