Synthesis and evaluation of heteroaryl-ketone derivatives as a novel class of VEGFR-2 inhibitors

被引：10

作者：

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

Katoch-Rouse, Reeti ^{[1
]}

Kiselyov, Alexander S. ^{[1
]}

Sherman, Dan ^{[1
]}

Ouyang, Xiaohu ^{[1
]}

Kim, Ki ^{[1
]}

Wang, Ying ^{[2
]}

Hadari, Yaron R. ^{[2
]}

Doody, Jacqueline F. ^{[2
]}

机构：

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

[2] ImClone Syst Inc, Dept Prot Sci, New York, NY 10014 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期

关键词：

angiogenesis; kinase inhibitor; vascular endothelial growth factor;

D O I：

10.1016/j.bmcl.2008.06.083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have discovered novel inhibitors of VEGFR-2 kinase with low nanomolar potency in both enzymatic and cell-based assays. Active series are heteroaryl-ketone compounds containing a central aromatic ring with either an indazolyl or indolyl keto group in the ortho orientation to the benzylic amine group (Fig. 1). The best compounds were demonstrated to be inactive against a small select panel of tyrosine and serine/threonine kinases with the exception of VEGFR-1 kinase, a close family member. In addition, the lead candidate 8 displayed acceptable exposure levels when administered orally to mice. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4344 / 4347

页数：4

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