Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent Aurora kinase inhibitors

Zhaoyang Meng; Bheemashankar A Kulkarni; Angela D Kerekes; Amit K Mandal; Sara J Esposite; David B Belanger; Panduranga Adulla Reddy; Andrea D Basso; Seema Tevar; Kimberly Gray; Jennifer Jones; Elizabeth B Smith; Ronald J Doll; M Arshad Siddiqui

doi:10.1016/j.bmcl.2010.10.008

Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent Aurora kinase inhibitors

Bioorg Med Chem Lett. 2011 Jan 1;21(1):592-8. doi: 10.1016/j.bmcl.2010.10.008. Epub 2010 Oct 12.

Authors

Zhaoyang Meng¹, Bheemashankar A Kulkarni, Angela D Kerekes, Amit K Mandal, Sara J Esposite, David B Belanger, Panduranga Adulla Reddy, Andrea D Basso, Seema Tevar, Kimberly Gray, Jennifer Jones, Elizabeth B Smith, Ronald J Doll, M Arshad Siddiqui

Affiliation

¹ Department of Chemistry, Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, United States. zhaoyang.meng@merck.com

PMID: 21075632
DOI: 10.1016/j.bmcl.2010.10.008

Abstract

Our continued effort toward the development of the imidazo[1,2-a]pyrazine scaffold as Aurora kinase inhibitors is described. Bioisosteric approach was applied to optimize the 8-position of the core. Several new potent Aurora A/B dual inhibitors, such as 25k and 25l, were identified.

MeSH terms

Animals
Aurora Kinase A
Aurora Kinases
Drug Evaluation, Preclinical
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacokinetics
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / metabolism
Pyrazines / chemical synthesis
Pyrazines / chemistry*
Pyrazines / pharmacokinetics
Rats

Substances

Imidazoles
Protein Kinase Inhibitors
Pyrazines
Aurka protein, rat
Aurora Kinase A
Aurora Kinases
Protein Serine-Threonine Kinases