6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3).
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).
Witherington
Jason
J
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. jason_witherington@gsk.com
Bordas
Vincent
V
Gaiba
Alessandra
A
Naylor
Antoinette
A
Rawlings
Anthony D
AD
Slingsby
Brian P
BP
Smith
David G
DG
Takle
Andrew K
AK
Ward
Robert W
RW
D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011725:Pyridines; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3