Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead optimization

Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.

Arylbenzothiazole derivatives originating from a vHTS approach were optimized to cellular activities on, for example, VEGFR2 down to EC50 = 60 nM.Figure optionsDownload as PowerPoint slide