Aza-stilbenes as potent and selective c-RAF inhibitors

Octerloney McDonald; Karen Lackey; Ronda Davis-Ward; Edgar Wood; Vicente Samano; Patrick Maloney; Felix Deanda; Robert Hunter

doi:10.1016/j.bmcl.2006.07.063

Aza-stilbenes as potent and selective c-RAF inhibitors

Bioorg Med Chem Lett. 2006 Oct 15;16(20):5378-83. doi: 10.1016/j.bmcl.2006.07.063. Epub 2006 Aug 4.

Authors

Octerloney McDonald¹, Karen Lackey, Ronda Davis-Ward, Edgar Wood, Vicente Samano, Patrick Maloney, Felix Deanda, Robert Hunter

Affiliation

¹ GlaxoSmithKline, Research Triangle Park, NC 27709, USA.

PMID: 16890436
DOI: 10.1016/j.bmcl.2006.07.063

Abstract

The synthesis of several novel aza-stilbene derivatives was carried out. The compounds were tested for their c-RAF enzyme inhibition. Compound 27 possesses significant potency against c-RAF and demonstrates selectivity over other protein kinases. A hypothesis for the binding mode, activity, and selectivity is proposed.

MeSH terms

Aza Compounds / chemical synthesis
Aza Compounds / chemistry
Aza Compounds / pharmacology*
Binding Sites
Enzyme Activation / drug effects
Models, Molecular
Molecular Structure
Protein Conformation
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-raf / antagonists & inhibitors*
Stereoisomerism
Stilbenes / chemical synthesis
Stilbenes / chemistry
Stilbenes / pharmacology*
Structure-Activity Relationship

Substances

Aza Compounds
Protein Kinase Inhibitors
Stilbenes
Proto-Oncogene Proteins c-raf