Synthesis of novel histamine H4 receptor antagonists

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1156-9. doi: 10.1016/j.bmcl.2011.11.098. Epub 2011 Dec 1.

Abstract

This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution.

MeSH terms

  • Animals
  • Azabicyclo Compounds / chemical synthesis
  • Azabicyclo Compounds / chemistry
  • Azabicyclo Compounds / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*
  • Rats
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Azabicyclo Compounds
  • HRH4 protein, human
  • Pyrrolidines
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4