The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase inhibitors.

Abstract

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to tumorigenesis. As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Herein, we describe our efforts toward the development of a potent, pan-Pim inhibitor. The synthesis and hit-to-lead SAR development from a 3-(pyrazin-2-yl)-1H-indazole derived hit 2 to the identification of a series of potent, pan-Pim inhibitors such as 13o are described.

• Authors: Hui-Ling Wang, Victor J Cee, Frank Chavez Jr, Brian A Lanman, Anthony B Reed, Bin Wu, Nadia Guerrero, J Russell Lipford, Christine Sastri, Jeff Winston, Kristin L Andrews, Xin Huang, Matthew R Lee, Christopher Mohr, Yang Xu, Yihong Zhou, Andrew S Tasker
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 4 Pg. 834-40 (Feb 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 25597005 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Indazoles
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-pim-1
• proto-oncogene proteins pim

Topics

• Drug Discovery
• Humans
• Indazoles (chemistry, pharmacology)
• Protein Kinase Inhibitors (chemistry, pharmacology)
• Proto-Oncogene Proteins c-pim-1 (antagonists & inhibitors)
• Structure-Activity Relationship