Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold

被引：71
|
作者：
Shahin, Mai I. [1 ]
Abou El Ella, Dalal A. [1 ]
Ismail, Nasser S. M. [1 ]
Abouzid, Khaled A. M. [1 ]
机构：
[1] Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt
来源：
BIOORGANIC CHEMISTRY | 2014年 / 56卷
关键词：
VEGFR-2; Kinase; Type-II; Quinoxaline; Docking study; TYROSINE KINASE INHIBITORS; CANCER-THERAPY; POTENT; DERIVATIVES; BINDING; CONFORMATIONS; SUBSTITUTION; RECEPTORS; REAGENTS; TARGETS;
D O I：
10.1016/j.bioorg.2014.05.010
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：
In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3-oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码：16 / 26
页数：11
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