title: RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation.
abstract: (+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in rodent models of angiogenesis upon oral administration.
authors.affiliation: Hoffmann-La Roche Inc., 340 Kingsland Str., Nutley, NJ 07110, USA. lee.mcdermott@roche.com
authors.forename: Lee A
authors.initials: LA
authors.lastname: McDermott
authors.forename: Mary
authors.initials: M
authors.lastname: Simcox
authors.forename: Brian
authors.initials: B
authors.lastname: Higgins
authors.forename: Tom
authors.initials: T
authors.lastname: Nevins
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kolinsky
authors.forename: Melissa
authors.initials: M
authors.lastname: Smith
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Jia K
authors.initials: JK
authors.lastname: Li
authors.forename: Yingsi
authors.initials: Y
authors.lastname: Chen
authors.forename: June
authors.initials: J
authors.lastname: Ke
authors.forename: Navita
authors.initials: N
authors.lastname: Mallalieu
authors.forename: Tom
authors.initials: T
authors.lastname: Egan
authors.forename: Stan
authors.initials: S
authors.lastname: Kolis
authors.forename: Aruna
authors.initials: A
authors.lastname: Railkar
authors.forename: Louise
authors.initials: L
authors.lastname: Gerber
authors.forename: Kin-Chun
authors.initials: KC
authors.lastname: Luk
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy; D005260:Female; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; C506187:RO4383596; D017468:Receptors, Fibroblast Growth Factor; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2