Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II.
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.
Duncton
Matthew A J
MA
Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA. mattduncton@yahoo.com
Piatnitski
Evgueni L
EL
Katoch-Rouse
Reeti
R
Smith
Leon M
LM
Kiselyov
Alexander S
AS
Milligan
Daniel L
DL
Balagtas
Chris
C
Wong
Wai C
WC
Kawakami
Joel
J
Doody
Jacqueline F
JF
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*
D007546:Isoquinolines; D010793:Phthalazines; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2