5-Aryl-4-carboxamide-1,3-oxazoles: potent and selective GSK-3 inhibitors

Gabriella Gentile; Giancarlo Merlo; Alfonso Pozzan; Giovanni Bernasconi; Benjamin Bax; Paul Bamborough; Angela Bridges; Paul Carter; Margarete Neu; Gang Yao; Caroline Brough; Geoffrey Cutler; Aaron Coffin; Svetlana Belyanskaya

doi:10.1016/j.bmcl.2012.01.034

5-Aryl-4-carboxamide-1,3-oxazoles: potent and selective GSK-3 inhibitors

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1989-94. doi: 10.1016/j.bmcl.2012.01.034. Epub 2012 Jan 21.

Authors

Gabriella Gentile¹, Giancarlo Merlo, Alfonso Pozzan, Giovanni Bernasconi, Benjamin Bax, Paul Bamborough, Angela Bridges, Paul Carter, Margarete Neu, Gang Yao, Caroline Brough, Geoffrey Cutler, Aaron Coffin, Svetlana Belyanskaya

Affiliation

¹ Department of Medicinal Chemistry, Neuroscience Centre of Excellence of Drug Discovery, GlaxoSmithKline, Via A Fleming 4, 37135 Verona, Italy.

PMID: 22310227
DOI: 10.1016/j.bmcl.2012.01.034

Abstract

5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK-3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described.

MeSH terms

Animals
Bipolar Disorder / drug therapy
Brain / metabolism
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / metabolism
Humans
Models, Molecular
Oxazoles / chemical synthesis
Oxazoles / chemistry*
Oxazoles / pharmacokinetics
Oxazoles / pharmacology*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Protein Kinase Inhibitors / pharmacology*
Rats
Structure-Activity Relationship

Substances

Oxazoles
Protein Kinase Inhibitors
Glycogen Synthase Kinase 3