title: Synthesis and evaluation of novel heterocyclic inhibitors of GSK-3.
abstract: A set of novel heterocyclic pyrimidyl hydrazones has been synthesized as inhibitors of glycogen synthase kinase-3 (GSK-3) with the most active exhibiting low nanomolar activity. Quantum mechanical calculations indicate that of the conformational factors that could determine binding affinity, the planarity of the phenyl ring in relation to the central core and the conformation of the hydrazone chain may be the most influential.
authors.affiliation: Research & Development, GlaxoSmithKline, Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA. terry.l.smalley@gsk.com
authors.forename: Terrence L
authors.initials: TL
authors.lastname: Smalley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peat
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Boucheron
authors.forename: Scott
authors.initials: S
authors.lastname: Dickerson
authors.forename: Dulce
authors.initials: D
authors.lastname: Garrido
authors.forename: Frank
authors.initials: F
authors.lastname: Preugschat
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schweiker
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Thomson
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Wang
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006834:Hydrazines / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D006834:Hydrazines; D038362:Glycogen Synthase Kinase 3