Novel imidazo[1,2-a]pyridine based inhibitors of the IGF-1 receptor tyrosine kinase: optimization of the aniline

Richard Ducray; Clifford D Jones; Frederic H Jung; Iain Simpson; Jon Curwen; Martin Pass

doi:10.1016/j.bmcl.2011.06.090

Novel imidazo[1,2-a]pyridine based inhibitors of the IGF-1 receptor tyrosine kinase: optimization of the aniline

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4702-4. doi: 10.1016/j.bmcl.2011.06.090. Epub 2011 Jun 25.

Authors

Richard Ducray¹, Clifford D Jones, Frederic H Jung, Iain Simpson, Jon Curwen, Martin Pass

Affiliation

¹ AstraZeneca, Oncology Innovative Medicines, Centre de recherches, Z.I. Pompelle, 51689 Reims Cedex 2, France. richard.ducray@astrazeneca.com

PMID: 21764307
DOI: 10.1016/j.bmcl.2011.06.090

Abstract

Following the discovery of imidazopyridine 1 as a potent IGF-1R tyrosine kinase inhibitor, the aniline part has been modified with the aim to optimize the properties of this series. The structure-activity relationships against IGF-1R kinase activity as well as inhibition of the hERG ion channel are discussed.

MeSH terms

Aniline Compounds / chemical synthesis
Aniline Compounds / chemistry
Aniline Compounds / pharmacology*
Drug Discovery
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
Humans
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology*
Receptor, IGF Type 1 / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship

Substances

Aniline Compounds
Ether-A-Go-Go Potassium Channels
Protein Kinase Inhibitors
Pyridines
Receptor, IGF Type 1
imidazo(1,2-a)pyridine
aniline