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

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.

Graphical abstractThe design of a new kinase inhibitor scaffold 1 based on known VEGF-R2 kinase inhibitors is described. The series designed to be inhibitors of VEGF-R2 kinase were synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, initial SAR, and in vivo efficacy of the series are discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide