2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines

Renate Determann; Jan Dreher; Knut Baumann; Lutz Preu; Peter G Jones; Frank Totzke; Christoph Schächtele; Michael H G Kubbutat; Conrad Kunick

doi:10.1016/j.ejmech.2012.04.007

2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines

Eur J Med Chem. 2012 Jul:53:254-63. doi: 10.1016/j.ejmech.2012.04.007. Epub 2012 Apr 14.

Authors

Renate Determann¹, Jan Dreher, Knut Baumann, Lutz Preu, Peter G Jones, Frank Totzke, Christoph Schächtele, Michael H G Kubbutat, Conrad Kunick

Affiliation

¹ Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.

PMID: 22560627
DOI: 10.1016/j.ejmech.2012.04.007

Abstract

2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Models, Molecular
Protein Conformation
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology*

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Pyrimidines