Synthesis and evaluation of novel heterocyclic inhibitors of GSK-3

Terrence L Smalley Jr; Andrew J Peat; Joyce A Boucheron; Scott Dickerson; Dulce Garrido; Frank Preugschat; Stephanie L Schweiker; Stephen A Thomson; Tony Y Wang

doi:10.1016/j.bmcl.2006.01.057

Synthesis and evaluation of novel heterocyclic inhibitors of GSK-3

Bioorg Med Chem Lett. 2006 Apr 15;16(8):2091-4. doi: 10.1016/j.bmcl.2006.01.057. Epub 2006 Feb 7.

Authors

Terrence L Smalley Jr¹, Andrew J Peat, Joyce A Boucheron, Scott Dickerson, Dulce Garrido, Frank Preugschat, Stephanie L Schweiker, Stephen A Thomson, Tony Y Wang

Affiliation

¹ Research & Development, GlaxoSmithKline, Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA. terry.l.smalley@gsk.com

PMID: 16460937
DOI: 10.1016/j.bmcl.2006.01.057

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.

Publication types

Evaluation Study

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / pharmacology
Hydrazines / chemical synthesis
Hydrazines / pharmacology
Inhibitory Concentration 50
Models, Chemical
Stereoisomerism

Substances

Enzyme Inhibitors
Heterocyclic Compounds
Hydrazines
Glycogen Synthase Kinase 3