2-((1H-azol-1-yl)methyl)-N-arylbenzamides:: Novel dual inhibitors of VEGFR-1/2 kinases

被引：17

作者：

Kiselyov, AS

Semenova, M

Semenov, VV

Piatnitski, E

机构：

[1] Chem Divers Inc, Small Mol Drug Discovery, San Diego, CA 92121 USA

[2] Russian Acad Sci, Inst Dev Biol, Moscow 119334, Russia

[3] Russian Acad Sci, ND Zelinskii Organ Chem Inst, Moscow 117913, Russia

[4] ImClone Syst, Small Mol Drug Discovery, New York, NY 10014 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 06期

关键词：

vascular endothelial growth factor receptor 2; receptor tyrosine kinase; dual kinase inhibitor; angiogenesis; 2-((1H-azol-1-yl)methyl)-N-arylbenzyl amides;

D O I：

10.1016/j.bmcl.2005.11.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel potent derivatives of (azol-1-yl)methyl-N-arylbenzamides with improved solubility (>3 mM) are described as ATP-competitive inhibitors of vascular endothelial growth factor receptor 2 (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity reaching IC50 < 100 nM in the enzymatic assay. The compounds also inhibit the related tyrosine kinase, VEGFR-1, with similar potencies. Several compounds containing bulky lipophilic substituents at the benzamide pharmacophore yielded 10- to 17-fold selectivity for the VEGFR-2 versus VEGFR-1 kinase. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1726 / 1730

页数：5

共 18 条

[1]

ALTMANN KH, 2005, Patent No. 6878720

[2]

Berman H.M., 2000, Protein Data Bank, P235

[3] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis [J].