Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors

David B Belanger; Patrick J Curran; Alan Hruza; Johannes Voigt; Zhaoyang Meng; Amit K Mandal; M Arshad Siddiqui; Andrea D Basso; Kimberly Gray

doi:10.1016/j.bmcl.2010.07.008

Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5170-4. doi: 10.1016/j.bmcl.2010.07.008. Epub 2010 Jul 8.

Authors

David B Belanger¹, Patrick J Curran, Alan Hruza, Johannes Voigt, Zhaoyang Meng, Amit K Mandal, M Arshad Siddiqui, Andrea D Basso, Kimberly Gray

Affiliation

¹ Department of Chemistry, Merck Research Laboratories, Cambridge, MA 02141, USA. david.belanger@merck.com

PMID: 20674350
DOI: 10.1016/j.bmcl.2010.07.008

Abstract

The synthesis and structure-activity relationships (SAR) of novel, potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed. Compound 10i was identified as lead compound with a promising overall profile.

MeSH terms

Aurora Kinases
Blood Proteins / metabolism
Crystallography, X-Ray
Drug Discovery
Flow Cytometry
Humans
Imidazoles / chemistry
Imidazoles / metabolism
Imidazoles / pharmacology*
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / metabolism
Protein Kinase Inhibitors / pharmacology*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Pyrazines / chemistry
Pyrazines / metabolism
Pyrazines / pharmacology*
Structure-Activity Relationship

Substances

Blood Proteins
Imidazoles
Protein Kinase Inhibitors
Pyrazines
Aurora Kinases
Protein Serine-Threonine Kinases