Discovery of novel VEGFR-2 inhibitors. Part II: Biphenyl urea incorporated with salicylaldoxime

被引：41

作者：

Gao, Hongping ^{[1
]}

Su, Ping ^{[1
]}

Shi, Yaling ^{[1
]}

Shen, Xiuxiu ^{[1
]}

Zhang, Yanmin ^{[1
]}

Dong, Jinyun ^{[1
]}

Zhang, Jie ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Pharm, Hlth Sci Ctr, Xian 710061, Shaanxi Provinc, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 90卷

基金：

中国国家自然科学基金;

关键词：

VEGFR-2; Biphenyl urea; Intramolecular hydrogen bond; Salicylaldoxime; RECEPTOR TYROSINE KINASE; BIOLOGICAL EVALUATION; ACID-DERIVATIVES; CANCER-CELLS; GROWTH; EGFR; ANGIOGENESIS; POTENT; AGENTS;

D O I：

10.1016/j.ejmech.2014.11.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular, 121, 12p and 12y exhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：232 / 240

页数：9

共 22 条

[1] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor [J].

Albert, DH ;

Tapang, P ;

Magoc, TJ ;

Pease, LJ ;

Reuter, DR ;

Wei, RQ ;

Li, JL ;

Guo, J ;

Bousquet, PF ;

Ghoreishi-Haack, NS ;

Wang, B ;

Bukofzer, GT ;

Wang, YC ;

Stavropoulos, JA ;

Hartandi, K ;

Niquette, AL ;

Soni, N ;

Johnson, EF ;

McCall, JO ;

Bouska, JJ ;

Luo, Y ;

Donawho, CK ;

Dai, YJ ;

Marcotte, PA ;

Glaser, KB ;

Michaelides, MR ;

Davidsen, SK .

MOLECULAR CANCER THERAPEUTICS, 2006, 5 (04) :995-1006

[2] SEQUENTIAL DIRECTED ORTHO METALATION BORONIC ACID CROSS-COUPLING REACTIONS - A GENERAL REGIOSPECIFIC ROUTE TO OXYGENATED DIBENZO[B,D]PYRAN-6-ONES RELATED TO ELLAGIC ACID [J].

ALO, BI ;

KANDIL, A ;

PATIL, PA ;

SHARP, MJ ;

SIDDIQUI, MA ;

SNIECKUS, V ;

JOSEPHY, PD .

JOURNAL OF ORGANIC CHEMISTRY, 1991, 56 (12) :3763-3768

[3]

Ciardiello F, 2001, CLIN CANCER RES, V7, P1459

[4] Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors [J].

de Castro Barbosa, Maria Leticia ;

Lima, Lidia Moreira ;

Tesch, Roberta ;

Sant'Anna, Carlos Mauricio R. ;

Totzke, Frank ;

Kubbutat, Michael H. G. ;

Schaechtele, Christoph ;

Laufer, Stefan A. ;

Barreiro, Eliezer J. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 71 :1-14

[5] Acryloylamino-salicylanilides as EGFR PTK inhibitors [J].

Deng, W ;

Guo, ZR ;

Guo, YS ;

Feng, ZQ ;

Jiang, Y ;

Chu, FM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (02) :469-472

[6] Solvent-Free and Safe Process for the Quantitative Production of Phosgene from Triphosgene by Deactivated Imino-Based Catalysts [J].

Eckert, Heiner ;

Auerweck, Johann .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (06) :1509-1513

[7] The biology of VEGF and its receptors [J].

Ferrara, N ;

Gerber, HP ;

LeCouter, J .

NATURE MEDICINE, 2003, 9 (06) :669-676

[8]

Fong TAT, 1999, CANCER RES, V59, P99

[9] PALLADIUM(O)-CATALYZED CROSS-COUPLING REACTION OF ALKOXYDIBORON WITH HALOARENES - A DIRECT PROCEDURE FOR ARYLBORONIC ESTERS [J].

ISHIYAMA, T ;

MURATA, M ;

MIYAURA, N .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (23) :7508-7510

[10] A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis [J].

Lu, Wen ;

Dai, Bingling ;

Ma, Weina ;

Zhang, Yanmin .

ONCOLOGY LETTERS, 2012, 4 (05) :1109-1113

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