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Published on: January 22, 2019
Isoindolinone ureas: a novel class of KDR kinase inhibitors
Michael L Curtin1, Robin R Frey, H Robin Heyman
1Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. mike.curtin@abbott.com
Abstract:
A series of substituted isoindolinone ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 14c, are potent inhibitors of KDR both enzymatically (< 50 nM) and cellularly < or = 100 nM). A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site.
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