Synthesis and evaluation of novel ligands for the histamine H₄ receptor based on a pyrrolo[2,3-d]pyrimidine scaffold

Bioorg Med Chem Lett. 2013 Jan 1;23(1):132-7. doi: 10.1016/j.bmcl.2012.10.139. Epub 2012 Nov 15.

Abstract

Starting from a known H(4)R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K(i)=0.5 μM), its lacks selectivity with a K(i) value for the hH(3)R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K(i) values of less than 1 μM at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Ligands*
  • Protein Binding
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / metabolism
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Histamine / chemistry
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H4
  • Structure-Activity Relationship

Substances

  • HRH4 protein, human
  • Ligands
  • Pyrimidines
  • Pyrroles
  • Pyrrolo(2,3-d)pyrimidine
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4