Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families.

Abstract

In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations.

• Authors: Michael L Curtin, Robin R Frey, H Robin Heyman, Niru B Soni, Patrick A Marcotte, Lori J Pease, Keith B Glaser, Terrance J Magoc, Paul Tapang, Daniel H Albert, Donald J Osterling, Amanda M Olson, Jennifer J Bouska, Zhiwen Guan, Lee C Preusser, James S Polakowski, Kent D Stewart, Chris Tse, Steven K Davidsen, Michael R Michaelides
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 9 Pg. 3208-12 (May 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22465635 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyridines
• Vascular Endothelial Growth Factor A
• thienopyridine
• Urea

Topics

• Animals
• Antineoplastic Agents (chemistry)
• Cell Line, Tumor
• Humans
• Mice
• Protein Kinase Inhibitors (chemistry, pharmacology)
• Pyridines (pharmacology)
• Urea (pharmacology)
• Vascular Endothelial Growth Factor A