Aryl–indolyl maleimides as inhibitors of CaMKIIδ. Part 1: SAR of the aryl region

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 34 nM to >20 μM and were dependant upon both the nature of the aryl group and the hydrogen bond donating potential of the maleimide ring. Key interactions with the kinase ATP site and hinge region were found to be consistent with homology modeling predictions.

Graphical abstractAryl-substituted maleimides were prepared and studied for their activity against CaMKIIδ. Inhibitory activities ranged from 34 nM to >20 μM. Key predicted interactions with the kinase ATP site and hinge region were confirmed.Figure optionsDownload full-size imageDownload as PowerPoint slide