Skip to main content
SpringerLink
Log in

Lead identification and optimization of diaminopyrimidines as histamine H4 receptor ligands

  • Short Communication
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

The human histamine H4 receptor (hH4R) is a promising new target in the therapy of inflammatory or immune system diseases.

Methods

For the development of new hH4R ligands, a broad virtual screening was performed and two hits were identified. Their annelated heterocyclic core was optimized with regard to affinity and potency.

Results

Pharmacological characterization of the resulting diaminopyrimidines revealed different agonist and antagonist properties within the same scaffold.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Zampeli E, Tiligada E. The role of histamine H4 receptor in immune and inflammatory disorders. Br J Pharmacol. 2009;157:24–33.

    Article  CAS  PubMed  Google Scholar 

  2. Kiss R, Keserü GM. Histamine H4 receptor ligands and their potential therapeutic applications. Expert Opin Ther Pat. 2009;19:119–35.

    Article  CAS  PubMed  Google Scholar 

  3. Schneider G, Neidhart W, Giller T, Schmid G. “Scaffold-hopping” by topological pharmacophore search: a contribution to virtual screening. Angew Chem Int Ed. 1999;38:2894–6.

    Article  CAS  Google Scholar 

  4. Schneider EH, Schnell D, Papa D, Seifert R. High constitutive activity and a G protein-independent high-affinity state of the human histamine H4 receptor. Biochemistry. 2009;48:1424–38.

    Article  CAS  PubMed  Google Scholar 

  5. Rodionov VO, Fokin VV, Finn MG. Mechanism of the ligand-free Cu(I)-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed. 2005;44:2210–5.

    Article  CAS  Google Scholar 

  6. Luo G, Chen L, Poindexter GS. Microwave-assisted synthesis of aminopyrimidines. Tetrahedron Lett. 2002;43:5739–42.

    Article  CAS  Google Scholar 

  7. Tanrikulu Y, Proschak E, Werner T, Geppert T, Todoroff N, Klenner A, et al. Homology model adjustment and ligand screening with a pseudoreceptor of the human histamine H4 receptor. ChemMedChem. 2009;4:820–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was awarded second prize at the EHRS meeting 2009 in the “Arthur A Hancock Young Investigator Award” sponsored by Abbott and was supported by the European COST Action BM0806 “Recent advances in histamine receptor H4R research” and the LOEWE OSF initiative.

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry, ZAFES/LiFF/CMP/OSF, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany

    K. Sander, T. Kottke & H. Stark

  2. Institute of Organic Chemistry and Chemical Biology, ZAFES/LiFF/CMP, Johann Wolfgang Goethe University, Siesmayerstr. 70, 60323, Frankfurt, Germany

    E. Proschak, Y. Tanrikulu & G. Schneider

  3. Department of Pharmacology and Toxicology, University of Regensburg, Universitätsstr. 31, 93053, Regensburg, Germany

    E. H. Schneider

  4. Institute of Pharmacology, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    R. Seifert

Authors
  1. K. Sander
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Kottke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Proschak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Tanrikulu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. H. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Seifert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Stark
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Stark.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sander, K., Kottke, T., Proschak, E. et al. Lead identification and optimization of diaminopyrimidines as histamine H4 receptor ligands. Inflamm. Res. 59 (Suppl 2), 249–251 (2010). https://doi.org/10.1007/s00011-009-0143-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-009-0143-2

Keywords

Search

Navigation