title: Thienopyridine urea inhibitors of KDR kinase.
abstract: A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. robin.heyman@abbott.com
authors.forename: H Robin
authors.initials: HR
authors.lastname: Heyman
authors.forename: Robin R
authors.initials: RR
authors.lastname: Frey
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: 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: Melinda
authors.initials: M
authors.lastname: Yates
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bouska
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Albert
authors.forename: Candace L
authors.initials: CL
authors.lastname: Black-Schaefer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dandliker
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Paul
authors.initials: P
authors.lastname: Rafferty
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
authors.forename: Michael L
authors.initials: ML
authors.lastname: Curtin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D004958:Estradiol; D005260:Female; D051379:Mice; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014591:Uterine Diseases / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D011725:Pyridines; C446540:thienopyridine; D004958:Estradiol; D014508:Urea; D040301:Vascular Endothelial Growth Factor Receptor-2