Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups

被引：21

作者：

Gaudette, Frederic ^{[1
]}

Raeppel, Stephane ^{[1
]}

Nguyen, Hannah ^{[2
]}

Beaulieu, Normand ^{[2
]}

Beaulieu, Carole ^{[2
]}

Dupont, Isabelle ^{[2
]}

Macleod, A. Robert ^{[2
]}

Besterman, Jeffrey M. ^{[2
]}

Vaisburg, Arkadii ^{[1
]}

机构：

[1] MethylGene Inc, Dept Med Chem, Montreal, PQ H4S 2A1, Canada

[2] MethylGene Inc, Dept Cell Biol & Pharmacol, Montreal, PQ H4S 2A1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

VEGFR2/KDR; c-Met; RTK inhibitors; Amide isostere; Angiogenesis; PARTIALLY MODIFIED RETRO; C-MET; CATHEPSIN-K; CANCER; GROWTH; TARGET; ANGIOGENESIS;

D O I：

10.1016/j.bmcl.2009.12.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of malonamide-type dual VEGFR2/c-Met inhibitors in which one of the amide bonds was replaced by an amide isostere-a trifluoroethylamine unit, was designed, synthesized, and evaluated for their enzymatic and cellular inhibition of VEGFR2 and c-Met enzymes. Optimization of these molecular entities resulted in identification of potent and selective inhibitors of VEGFR2 enzyme. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：848 / 852

页数：5

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