Discovery of pyrazolo[1,5-a]pyrimidine-based Pim inhibitors: a template-based approach

Michael P Dwyer; Kartik Keertikar; Kamil Paruch; Carmen Alvarez; Marc Labroli; Cory Poker; Thierry O Fischmann; Rosemary Mayer-Ezell; Richard Bond; Yan Wang; Rita Azevedo; Timothy J Guzi

doi:10.1016/j.bmcl.2013.08.110

Discovery of pyrazolo[1,5-a]pyrimidine-based Pim inhibitors: a template-based approach

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6178-82. doi: 10.1016/j.bmcl.2013.08.110. Epub 2013 Sep 7.

Authors

Michael P Dwyer¹, Kartik Keertikar, Kamil Paruch, Carmen Alvarez, Marc Labroli, Cory Poker, Thierry O Fischmann, Rosemary Mayer-Ezell, Richard Bond, Yan Wang, Rita Azevedo, Timothy J Guzi

Affiliation

¹ Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. Electronic address: michael.dwyer@merck.com.

PMID: 24091081
DOI: 10.1016/j.bmcl.2013.08.110

Abstract

The synthesis and hit-to-lead SAR development from a pyrazolo[1,5-a]pyrimidine-derived hit 5 to the identification of a series of potent, pan-Pim inhibitors such as 11j are described.

Keywords: Pan–Pim kinase; pyrazolo[1,5-a]pyrimidine.

MeSH terms

Humans
Protein Binding
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1 / chemistry
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Proto-Oncogene Proteins c-pim-1
proto-oncogene proteins pim