Highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase

Noel A Powell; Jennifer K Hoffman; Fred L Ciske; Michael D Kaufman; Jeffrey T Kohrt; John Quin 3rd; Derek J Sheehan; Amy Delaney; Sangita M Baxi; Cornel Catana; Patrick McConnell; Jeff Ohren; Lisa A Perrin; Jeremy J Edmunds

doi:10.1016/j.bmcl.2012.12.013

Highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase

Bioorg Med Chem Lett. 2013 Feb 15;23(4):1046-50. doi: 10.1016/j.bmcl.2012.12.013. Epub 2012 Dec 20.

Authors

Noel A Powell¹, Jennifer K Hoffman, Fred L Ciske, Michael D Kaufman, Jeffrey T Kohrt, John Quin 3rd, Derek J Sheehan, Amy Delaney, Sangita M Baxi, Cornel Catana, Patrick McConnell, Jeff Ohren, Lisa A Perrin, Jeremy J Edmunds

Affiliation

¹ Pfizer Global Research & Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. [email protected]

PMID: 23312472
DOI: 10.1016/j.bmcl.2012.12.013

Abstract

We report the SAR around a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. 2-Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity, while 2-aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity.

MeSH terms

Amides / chemistry
Amides / pharmacology
Animals
Humans
Mice
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Structure-Activity Relationship
Substrate Specificity

Substances

Amides
Protein Kinase Inhibitors
Pyrimidines
2,4-diaminopyrimidine
Receptor Protein-Tyrosine Kinases
TYRO3 protein, human