title: Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families.
abstract: In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations.
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: Niru B
authors.initials: NB
authors.lastname: Soni
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Marcotte
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Pease
authors.forename: Keith B
authors.initials: KB
authors.lastname: Glaser
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Magoc
authors.forename: Paul
authors.initials: P
authors.lastname: Tapang
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Albert
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Osterling
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Olson
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bouska
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Guan
authors.forename: Lee C
authors.initials: LC
authors.lastname: Preusser
authors.forename: James S
authors.initials: JS
authors.lastname: Polakowski
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Chris
authors.initials: C
authors.lastname: Tse
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; C446540:thienopyridine; D014508:Urea