Design and synthesis of close analogs of LCRF-0004, a potent and selective RON receptor tyrosine kinase inhibitor

Stéphane L Raeppel; Franck Raeppel; Eric Therrien

doi:10.1016/j.bmcl.2015.04.056

Design and synthesis of close analogs of LCRF-0004, a potent and selective RON receptor tyrosine kinase inhibitor

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2527-31. doi: 10.1016/j.bmcl.2015.04.056. Epub 2015 Apr 23.

Authors

Stéphane L Raeppel¹, Franck Raeppel², Eric Therrien²

Affiliations

¹ ChemRF Laboratories, 3194 rue Claude-Jodoin, Montréal, QC H1Y 3M2, Canada. Electronic address: stephane.raeppel@gmail.com.
² ChemRF Laboratories, 3194 rue Claude-Jodoin, Montréal, QC H1Y 3M2, Canada.

PMID: 25953155
DOI: 10.1016/j.bmcl.2015.04.056

Abstract

New carboxamide head group analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent and selective inhibitors of RON enzyme versus c-Met RTK were obtained.

Keywords: Head group; Oncology; RON; RTK inhibitors; Thieno[3,2-b]pyridine scaffold; c-Met.

MeSH terms

Amides / chemistry
Binding Sites
Drug Design*
Heterocyclic Compounds, 2-Ring / chemical synthesis*
Heterocyclic Compounds, 2-Ring / chemistry
Humans
Molecular Docking Simulation
Protein Binding
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / metabolism
Protein Structure, Tertiary
Proto-Oncogene Proteins c-met / antagonists & inhibitors
Proto-Oncogene Proteins c-met / metabolism
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Receptor Protein-Tyrosine Kinases / metabolism

Substances

Amides
Heterocyclic Compounds, 2-Ring
LCRF-0004
Protein Kinase Inhibitors
Pyrazoles
Proto-Oncogene Proteins c-met
RON protein
Receptor Protein-Tyrosine Kinases