Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity

被引：39

作者：

Dao, Pascal ^{[1
]}

Lietha, Daniel ^{[2
]}

Etheve-Quelquejeu, Melanie ^{[1
]}

Garbay, Christiane ^{[1
]}

Chen, Huixiong ^{[1
]}

机构：

[1] Univ Paris 05, CNRS UMR8601, PRES Sorbonne Paris Cite, UFR Biomed, 45 Rue St Peres, F-75270 Paris 06, France

[2] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Cell Signalling & Adhes Grp, Calle Melchor Fernandez Almagro 3, Madrid 28029, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 08期

关键词：

FAK inhibitors; Synthesis; 1,2,4-Triazines; Anti-cancer activity; Molecular docking; FOCAL ADHESION KINASE; PHASE-I; CANCER; DERIVATIVES; TAE226;

D O I：

10.1016/j.bmcl.2017.02.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1,3,5-triazinic inhibitors of focal adhesion kinase (FAK) has recently been shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. In this report, we designed and synthesized a series of new compounds containing a 1,2,4-triazine core as novel scaffold for FAK inhibitors. These compounds displayed 10-7M IC50 values, and the best one showed IC50 value of 0.23 mu M against FAK enzymatic activity. Among them, several inhibitors potently inhibited the proliferation of glioblastoma (U-87MG) and colon (HCT-116) cancer cell lines. Docking of compound 10 into the active site of the FAK kinase was performed to explore its potential binding mode. (C) 2017 Published by Elsevier Ltd.

引用

页码：1727 / 1730

页数：4

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