2. Academic Validation
  3. Arylphthalazines as potent, and orally bioavailable inhibitors of VEGFR-2

Arylphthalazines as potent, and orally bioavailable inhibitors of VEGFR-2

  • Bioorg Med Chem. 2009 Jan 15;17(2):731-40. doi: 10.1016/j.bmc.2008.11.049.
Matthew A J Duncton 1,  Eugene L Piatnitski Chekler,  Reeti Katoch-Rouse,  Dan Sherman,  Wai C Wong,  Leon M Smith 2nd,  Joel K Kawakami,  Alexander S Kiselyov,  Daniel L Milligan,  Chris Balagtas,  Yaron R Hadari,  Ying Wang,  Sheetal N Patel,  Robin L Rolster,  James R Tonra,  David Surguladze,  Stan Mitelman,  Paul Kussie,  Peter Bohlen,  Jacqueline F Doody
Affiliations

Affiliation

  • 1 ImClone Systems, Inc., 180 Varick Street, New York, NY 10014, USA. mattduncton@yahoo.com
PMID: 19101155 DOI: 10.1016/j.bmc.2008.11.049
Abstract

A series of arylphthalazine derivatives were synthesized and evaluated as antagonists of VEGF receptor II (VEGFR-2). IM-094482 57, which was prepared in two steps from commercially available starting Materials, was found to be a potent inhibitor of VEGFR-2 in enzymatic, cellular and mitogenic assays (comparable activity to ZD-6474). Additionally, 57 inhibited the related receptor, VEGF receptor I (VEGFR-1), and showed excellent exposure when dosed orally to female CD-1 mice.

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