Isoindolinone ureas: a novel class of KDR kinase inhibitors

  • Bioorg Med Chem Lett. 2004 Sep 6;14(17):4505-9. doi: 10.1016/j.bmcl.2004.06.041.
Michael L Curtin  1 ,  Robin R Frey ,  H Robin Heyman ,  Kathy A 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
Affiliations
  • 1. Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. [email protected]
PMID: 15357981 DOI: 10.1016/j.bmcl.2004.06.041
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.