Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase

Evgueni L Piatnitski; Matthew A J Duncton; Alexander S Kiselyov; Reeti Katoch-Rouse; Dan Sherman; Daniel L Milligan; Chris Balagtas; Wai C Wong; Joel Kawakami; Jacqueline F Doody

doi:10.1016/j.bmcl.2005.07.064

Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase

Bioorg Med Chem Lett. 2005 Nov 1;15(21):4696-8. doi: 10.1016/j.bmcl.2005.07.064.

Authors

Evgueni L Piatnitski¹, Matthew A J Duncton, Alexander S Kiselyov, Reeti Katoch-Rouse, Dan Sherman, Daniel L Milligan, Chris Balagtas, Wai C Wong, Joel Kawakami, Jacqueline F Doody

Affiliation

¹ Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA.

PMID: 16143524
DOI: 10.1016/j.bmcl.2005.07.064

Abstract

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.

MeSH terms

Angiogenesis Inhibitors / chemical synthesis*
Angiogenesis Inhibitors / pharmacology
Inhibitory Concentration 50
Phthalazines / chemical synthesis*
Phthalazines / pharmacology
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
Structure-Activity Relationship
Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

Angiogenesis Inhibitors
Phthalazines
Protein Kinase Inhibitors
phthalazine
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2