Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase.
A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 microM in an HTRF enzymatic assay. These compounds are relatively selective against a small kinase panel.
Piatnitski
Evgueni L
EL
Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA.
Duncton
Matthew A J
MA
Kiselyov
Alexander S
AS
Katoch-Rouse
Reeti
R
Sherman
Dan
D
Milligan
Daniel L
DL
Balagtas
Chris
C
Wong
Wai C
WC
Kawakami
Joel
J
Doody
Jacqueline F
JF
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010793:Phthalazines / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; C043388:phthalazine; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2