6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)

Jason Witherington; Vincent Bordas; Alessandra Gaiba; Antoinette Naylor; Anthony D Rawlings; Brian P Slingsby; David G Smith; Andrew K Takle; Robert W Ward

doi:10.1016/s0960-894x(03)00646-2

6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3059-62. doi: 10.1016/s0960-894x(03)00646-2.

Authors

Jason Witherington¹, Vincent Bordas, Alessandra Gaiba, Antoinette Naylor, Anthony D Rawlings, Brian P Slingsby, David G Smith, Andrew K Takle, Robert W Ward

Affiliation

¹ Department of Medicinal Chemistry, Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. [email protected]

PMID: 12941333
DOI: 10.1016/s0960-894x(03)00646-2

Abstract

A series of 6-heteroaryl-pyrazolo[3,4-b]pyridines has been optimised to afford potent inhibitors of Glycogen Synthase Kinase-3 (GSK-3). These analogues display excellent selectivity over the closely related Cyclin Dependent Kinase-2 (CDK-2).

MeSH terms

Animals
CDC2-CDC28 Kinases / antagonists & inhibitors
Cyclin-Dependent Kinase 2
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Humans
Hydrogen Bonding
Inhibitory Concentration 50
Pyridines / chemical synthesis*
Pyridines / pharmacology
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Pyridines
CDC2-CDC28 Kinases
CDK2 protein, human
Cyclin-Dependent Kinase 2
Glycogen Synthase Kinase 3