Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II

Matthew A J Duncton; Evgueni L Piatnitski; Reeti Katoch-Rouse; Leon M Smith 2nd; Alexander S Kiselyov; Daniel L Milligan; Chris Balagtas; Wai C Wong; Joel Kawakami; Jacqueline F Doody

doi:10.1016/j.bmcl.2005.12.045

Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1579-81. doi: 10.1016/j.bmcl.2005.12.045. Epub 2005 Dec 28.

Authors

Matthew A J Duncton¹, Evgueni L Piatnitski, Reeti Katoch-Rouse, Leon M Smith 2nd, Alexander S Kiselyov, 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. [email protected]

PMID: 16386418
DOI: 10.1016/j.bmcl.2005.12.045

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.

MeSH terms

Fluoroimmunoassay
Humans
Inhibitory Concentration 50
Isoquinolines / chemical synthesis
Isoquinolines / pharmacology*
Phthalazines / chemical synthesis
Phthalazines / pharmacology*
Structure-Activity Relationship
Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Isoquinolines
Phthalazines
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2