Discovery of novel imidazo[1,2-a]pyridines as inhibitors of the insulin-like growth factor-1 receptor tyrosine kinase

Richard Ducray; Iain Simpson; Frederic H Jung; J Willem M Nissink; Peter W Kenny; Martina Fitzek; Graeme E Walker; Lara T Ward; Kevin Hudson

doi:10.1016/j.bmcl.2011.06.093

Discovery of novel imidazo[1,2-a]pyridines as inhibitors of the insulin-like growth factor-1 receptor tyrosine kinase

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4698-701. doi: 10.1016/j.bmcl.2011.06.093. Epub 2011 Jun 29.

Authors

Richard Ducray¹, Iain Simpson, Frederic H Jung, J Willem M Nissink, Peter W Kenny, Martina Fitzek, Graeme E Walker, Lara T Ward, Kevin Hudson

Affiliation

¹ AstraZeneca, Oncology Innovative Medicines, Centre de Recherches, Z.I. Pompelle, 51689 Reims Cedex 2, France. [email protected]

PMID: 21775140
DOI: 10.1016/j.bmcl.2011.06.093

Abstract

We disclose a novel series of insulin-like growth factor-1 receptor kinase inhibitors based on the 3-(pyrimidin-4-yl)-imidazo[1,2-a]pyridine scaffold. The influence on the inhibitory activity of substitution on the imidazopyridine and at the C5 position of the pyrimidine is discussed. In the course of this optimization, we discovered a potent and selective inhibitor with suitable pharmacokinetics for oral administration.

MeSH terms

Animals
Dogs
Drug Discovery*
Humans
Mice
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology*
Rats
Receptor, IGF Type 1 / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Tissue Distribution

Substances

Protein Kinase Inhibitors
Pyridines
Receptor, IGF Type 1
imidazo(1,2-a)pyridine