title: Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors.
abstract: A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar(1)) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range.
authors.affiliation: GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peat
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Boucheron
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
authors.forename: Dulce
authors.initials: D
authors.lastname: Garrido
authors.forename: Wendy
authors.initials: W
authors.lastname: Mills
authors.forename: Jennifer
authors.initials: J
authors.lastname: Peckham
authors.forename: Frank
authors.initials: F
authors.lastname: Preugschat
authors.forename: Terrence
authors.initials: T
authors.lastname: Smalley
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schweiker
authors.forename: Jayme R
authors.initials: JR
authors.lastname: Wilson
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Wang
authors.forename: Huiqiang Q
authors.initials: HQ
authors.lastname: Zhou
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Thomson
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D038362:Glycogen Synthase Kinase 3