title: 5-aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).
abstract: Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography.
authors.affiliation: Department of Medicinal Chemistry, Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline Research Limited, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK. jason_witherington@gsk.com
authors.forename: Jason
authors.initials: J
authors.lastname: Witherington
authors.forename: Vincent
authors.initials: V
authors.lastname: Bordas
authors.forename: David
authors.initials: D
authors.lastname: Haigh
authors.forename: Deirdre M B
authors.initials: DM
authors.lastname: Hickey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ife
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Rawlings
authors.forename: Brian P
authors.initials: BP
authors.lastname: Slingsby
authors.forename: David G
authors.initials: DG
authors.lastname: Smith
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ward
mesh_terms: D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D011720:Pyrazoles; D011724:Pyridazines; D038362:Glycogen Synthase Kinase 3