7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity

Terry V Hughes; Stuart L Emanuel; Harold R O'Grady; Peter J Connolly; Catherine Rugg; Angel R Fuentes-Pesquera; Prabha Karnachi; Richard Alexander; Steven A Middleton

doi:10.1016/j.bmcl.2008.07.090

7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity

Bioorg Med Chem Lett. 2008 Sep 15;18(18):5130-3. doi: 10.1016/j.bmcl.2008.07.090. Epub 2008 Jul 26.

Authors

Terry V Hughes¹, Stuart L Emanuel, Harold R O'Grady, Peter J Connolly, Catherine Rugg, Angel R Fuentes-Pesquera, Prabha Karnachi, Richard Alexander, Steven A Middleton

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, L.L.C, PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA. hughe007@hotmail.com

PMID: 18718756
DOI: 10.1016/j.bmcl.2008.07.090

Abstract

A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed.

MeSH terms

Animals
Aurora Kinase A
Aurora Kinases
Combinatorial Chemistry Techniques
Drug Design
Indoles* / chemical synthesis
Indoles* / pharmacology
Mice
Models, Molecular
Molecular Structure
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Structure-Activity Relationship
Vascular Endothelial Growth Factors / metabolism
Xenograft Model Antitumor Assays

Substances

Indoles
Vascular Endothelial Growth Factors
Receptor Protein-Tyrosine Kinases
Aurka protein, mouse
Aurora Kinase A
Aurora Kinases
Protein Serine-Threonine Kinases