Design and synthesis of 6,6-fused heterocyclic amides as raf kinase inhibitors

Savithri Ramurthy; Abran Costales; Johanna M Jansen; Barry Levine; Paul A Renhowe; Cynthia M Shafer; Sharadha Subramanian

doi:10.1016/j.bmcl.2011.12.112

Design and synthesis of 6,6-fused heterocyclic amides as raf kinase inhibitors

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1678-81. doi: 10.1016/j.bmcl.2011.12.112. Epub 2011 Dec 30.

Authors

Savithri Ramurthy¹, Abran Costales, Johanna M Jansen, Barry Levine, Paul A Renhowe, Cynthia M Shafer, Sharadha Subramanian

Affiliation

¹ Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, Emeryville, CA 94608, USA. savithri.ramurthy@novartis.com

PMID: 22264479
DOI: 10.1016/j.bmcl.2011.12.112

Abstract

Compounds belonging to several scaffolds-quinazolines, quinolines and quinoxalines-were designed and synthesized as Raf kinase inhibitors. Scaffolds were assessed for in vitro Braf(V600E) inhibition, and overall kinase selectivity. Pharmacokinetic parameters for one of the scaffolds were also determined.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology*
Binding Sites
Cells, Cultured
Drug Design*
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology
Humans
Models, Molecular
Molecular Structure
raf Kinases / antagonists & inhibitors*

Substances

Amides
Enzyme Inhibitors
Heterocyclic Compounds
raf Kinases