title: Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II.
abstract: A novel class of 1-(isoquinolin-5-yl)-4-arylamino-phthalazines is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC(50) as low as 0.017 microM in an HTRF enzymatic assay. The compounds also inhibit VEGFR-1, a related tyrosine kinase.
authors.affiliation: Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA. mattduncton@yahoo.com
authors.forename: Matthew A J
authors.initials: MA
authors.lastname: Duncton
authors.forename: Evgueni L
authors.initials: EL
authors.lastname: Piatnitski
authors.forename: Reeti
authors.initials: R
authors.lastname: Katoch-Rouse
authors.forename: Leon M
authors.initials: LM
authors.lastname: Smith
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Milligan
authors.forename: Chris
authors.initials: C
authors.lastname: Balagtas
authors.forename: Wai C
authors.initials: WC
authors.lastname: Wong
authors.forename: Joel
authors.initials: J
authors.lastname: Kawakami
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Doody
mesh_terms: D015200:Fluoroimmunoassay; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D010793:Phthalazines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D007546:Isoquinolines; D010793:Phthalazines; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2