title: Isoindolinone ureas: a novel class of KDR kinase inhibitors.
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.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. mike.curtin@abbott.com
authors.forename: Michael L
authors.initials: ML
authors.lastname: Curtin
authors.forename: Robin R
authors.initials: RR
authors.lastname: Frey
authors.forename: H Robin
authors.initials: HR
authors.lastname: Heyman
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Sarris
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Steinman
authors.forename: James H
authors.initials: JH
authors.lastname: Holmes
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bousquet
authors.forename: George A
authors.initials: GA
authors.lastname: Cunha
authors.forename: Maria D
authors.initials: MD
authors.lastname: Moskey
authors.forename: Asma A
authors.initials: AA
authors.lastname: Ahmed
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Pease
authors.forename: Keith B
authors.initials: KB
authors.lastname: Glaser
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D014508:Urea; D040301:Vascular Endothelial Growth Factor Receptor-2