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

被引：38

作者：

Duncton, Matthew A. J. ^{[1
]}

Chekler, Eugene L. Piatnitski ^{[1
]}

Katoch-Rouse, Reeti ^{[1
]}

Sherman, Dan ^{[1
]}

Wong, Wai C. ^{[1
]}

Smith, Leon M., II ^{[1
]}

Kawakami, Joel K. ^{[1
]}

Kiselyov, Alexander S. ^{[1
]}

Milligan, Daniel L. ^{[1
]}

Balagtas, Chris ^{[1
]}

Hadari, Yaron R. ^{[1
]}

Wang, Ying ^{[1
]}

Patel, Sheetal N. ^{[1
]}

Rolster, Robin L. ^{[1
]}

Tonra, James R. ^{[1
]}

Surguladze, David ^{[1
]}

Mitelman, Stan ^{[1
]}

Kussie, Paul ^{[1
]}

Bohlen, Peter ^{[1
]}

Doody, Jacqueline F. ^{[1
]}

机构：

[1] ImClone Syst Inc, New York, NY 10014 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 02期

关键词：

Arylphthalazine; Phthalazine; Inhibitor; VEGFR-2; KDR; Kinase; Angiogenesis; ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; METHYL ETHYL ETHERS; GENERAL-ANESTHETICS; TUMOR-GROWTH; ANTITUMOR-ACTIVITY; HIGHLY POTENT; DISCOVERY; ANGIOGENESIS; TARGETS;

D O I：

10.1016/j.bmc.2008.11.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：731 / 740

页数：10

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