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Isoindolinone ureas: a novel class of KDR kinase inhibitors

2004; Elsevier BV; Volume: 14; Issue: 17 Linguagem: Inglês

10.1016/j.bmcl.2004.06.041

1464-3405

Michael L. Curtin, Robin R. Frey, H. Robin Heyman, Kathy Sarris, Douglas H. Steinman, James H. Holmes, Peter F. Bousquet, George A. Cunha, Maria D. Moskey, Asma A. Ahmed, Lori J. Pease, Keith B. Glaser, Kent D. Stewart, Steven K. Davidsen, Michael R. Michaelides,

Signaling Pathways in Disease

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.