Tri- and tetrasubstituted imidazoles as p38α mitogen-activated protein kinase inhibitors

Stefan Laufer; Dominik Hauser; Thomas Stegmiller; Claudia Bracht; Kathrin Ruff; Verena Schattel; Wolfgang Albrecht; Pierre Koch

doi:10.1016/j.bmcl.2010.09.012

Tri- and tetrasubstituted imidazoles as p38α mitogen-activated protein kinase inhibitors

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6671-5. doi: 10.1016/j.bmcl.2010.09.012. Epub 2010 Sep 9.

Authors

Stefan Laufer¹, Dominik Hauser, Thomas Stegmiller, Claudia Bracht, Kathrin Ruff, Verena Schattel, Wolfgang Albrecht, Pierre Koch

Affiliation

¹ Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard Karls University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. stefan.laufer@uni-tuebingen.de

PMID: 20934337
DOI: 10.1016/j.bmcl.2010.09.012

Abstract

The synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles as potent p38α mitogen-activated protein kinase inhibitors is described. The trisubstituted imidazole series was found to be more potent than the tetrasubstituted imidazole series. Many of these compounds show low-nanomolar activities in the isolated p38α MAP kinase inhibition assay. The structure-activity relationships between these two series are different and not comparable.

MeSH terms

Imidazoles / chemistry
Imidazoles / pharmacology*
Models, Molecular
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

Imidazoles
Protein Kinase Inhibitors
p38 Mitogen-Activated Protein Kinases