6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors

Karen Coffman; Michael Brodney; James Cook; Lorraine Lanyon; Jayvardhan Pandit; Subas Sakya; Joel Schachter; Elaine Tseng-Lovering; Matthew Wessel

doi:10.1016/j.bmcl.2011.01.017

6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1429-33. doi: 10.1016/j.bmcl.2011.01.017. Epub 2011 Jan 11.

Authors

Karen Coffman¹, Michael Brodney, James Cook, Lorraine Lanyon, Jayvardhan Pandit, Subas Sakya, Joel Schachter, Elaine Tseng-Lovering, Matthew Wessel

Affiliation

¹ Pfizer Global Research and Development, Groton Laboratories, Groton, CT 06340, USA. [email protected]

PMID: 21295469
DOI: 10.1016/j.bmcl.2011.01.017

Abstract

The synthesis and structure-activity relationships for a novel series of 6-amino-4-(pyrimidin-4-yl)pyridones derived from a high throughput screening hit are discussed. Optimization of lead matter afforded compounds with good potency, selectivity and central nervous system (CNS) exposure.

MeSH terms

Central Nervous System / drug effects
Crystallography, X-Ray
Glycogen Synthase Kinases / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Pyridones / chemical synthesis*
Pyridones / chemistry
Pyridones / pharmacology
Structure-Activity Relationship

Substances

Protein Kinase Inhibitors
Pyridones
Glycogen Synthase Kinases