Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004

Franck Raeppel; Stéphane L Raeppel; Eric Therrien

doi:10.1016/j.bmcl.2015.07.080

Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004

Bioorg Med Chem Lett. 2015 Sep 15;25(18):3810-5. doi: 10.1016/j.bmcl.2015.07.080. Epub 2015 Jul 29.

Authors

Franck Raeppel¹, Stéphane L Raeppel², Eric Therrien¹

Affiliations

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

PMID: 26243370
DOI: 10.1016/j.bmcl.2015.07.080

Abstract

New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained.

Keywords: Head group; Molecular docking; Oncology; RON; RON homology model; RTK inhibitors; c-Met.

MeSH terms

Dose-Response Relationship, Drug
Drug Design*
Heterocyclic Compounds, 2-Ring / chemical synthesis
Heterocyclic Compounds, 2-Ring / chemistry
Heterocyclic Compounds, 2-Ring / pharmacology*
Humans
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Receptor Protein-Tyrosine Kinases / metabolism
Structure-Activity Relationship

Substances

Heterocyclic Compounds, 2-Ring
LCRF-0004
Protein Kinase Inhibitors
Pyrazoles
RON protein
Receptor Protein-Tyrosine Kinases