title: Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors.
abstract: Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
authors.affiliation: Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. yujia.dai@abbott.com
authors.forename: Yujia
authors.initials: Y
authors.lastname: Dai
authors.forename: Kresna
authors.initials: K
authors.lastname: Hartandi
authors.forename: Niru B
authors.initials: NB
authors.lastname: Soni
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Pease
authors.forename: David R
authors.initials: DR
authors.lastname: Reuter
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Olson
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Osterling
authors.forename: Stella Z
authors.initials: SZ
authors.lastname: Doktor
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Albert
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bouska
authors.forename: Keith B
authors.initials: KB
authors.lastname: Glaser
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Marcotte
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: D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014591:Uterine Diseases / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D014508:Urea; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor