Design and synthesis of 5,6-fused heterocyclic amides as Raf kinase inhibitors

Savithri Ramurthy; Mina Aikawa; Payman Amiri; Abran Costales; Ahmad Hashash; Johanna M Jansen; Song Lin; Sylvia Ma; Paul A Renhowe; Cynthia M Shafer; Sharadha Subramanian; Leonard Sung; Joelle Verhagen

doi:10.1016/j.bmcl.2011.04.023

Design and synthesis of 5,6-fused heterocyclic amides as Raf kinase inhibitors

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3286-9. doi: 10.1016/j.bmcl.2011.04.023. Epub 2011 Apr 14.

Authors

Savithri Ramurthy¹, Mina Aikawa, Payman Amiri, Abran Costales, Ahmad Hashash, Johanna M Jansen, Song Lin, Sylvia Ma, Paul A Renhowe, Cynthia M Shafer, Sharadha Subramanian, Leonard Sung, Joelle Verhagen

Affiliation

¹ Global Discovery Chemistry/Oncology and Exploratory Chemistry, Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA. savithri.ramurthy@novartis.com

PMID: 21543226
DOI: 10.1016/j.bmcl.2011.04.023

Abstract

Two scaffolds based on 5,6-fused heterocyclic backbones were designed and synthesized as Raf kinase inhibitors. The scaffolds were assessed for in vitro pan-Raf inhibition, activity in cell proliferation and target modulation assays, and pharmacokinetic parameters.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology
Binding Sites
Cell Proliferation
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
Models, Molecular
Molecular Structure
Structure-Activity Relationship
raf Kinases / antagonists & inhibitors*

Substances

Amides
Enzyme Inhibitors
Heterocyclic Compounds
raf Kinases