Design, Synthesis and Antitumor Activities of Bis-arylureas and Bis-arylamides Based on1H-benzo[d]imidazole Moiety as Novel BRaf<sup>V600E</sup>/VEGFR2 Dual inhibitors

ISSN: 1875-628X (Online)
ISSN: 1570-1808 (Print)


Volume 11, 10 Issues, 2014


Download PDF Flyer




Letters in Drug Design & Discovery

Aims & ScopeAbstracted/Indexed in


Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK
Email: lddd@benthamscience.org

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 0.961
5 - Year: 0.917

Design, Synthesis and Antitumor Activities of Bis-arylureas and Bis-arylamides Based on1H-benzo[d]imidazole Moiety as Novel BRafV600E/VEGFR2 Dual inhibitors

Author(s): Weimin Yang, Yadong Chen, Yanmin Zhang, Sanzhi Tang, Hongli Chen, Weifang Tang and Tao Lu

Affiliation: School of Basic Sciences, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.

Abstract

A series of bis-arylurea and bis-arylamide derivatives based on 1H-benzo[d]imidazole moiety were designed, synthesized and evaluated as DFG-out B-RafV600E/VEGFR2 dual inhibitors. Compound 4a as the most potent compound displayed potential dual kinase inhibitory activities against B-RafV600E and VEGFR2 with IC50 values of 57.8 nM and 0.48 μM, as well as effective cellular antiproliferative potencies against A375 and HUVEC with IC50 values of 3.62 µM and 12.46 µM. 4a was also progressed to in vivo profiling, which exhibited similarly equivalent tumor growth inhibition (T/C = 17.99%) in human melanoma A375 (B-RafV600E) xenograft model by contrast to Sorafenib (T/C = 16.49%) without body weight loss.




Keywords: Antitumor, B-RafV600E, DFG-out type, dual inhibitors, 1H-benzo[d]imidazole moiety, VEGFR2.

Purchase Online Order Reprints Order Eprints Rights and Permissions

  
  



Article Details

Volume: 11
Issue Number: 9
First Page: 1079
Last Page: 1089
Page Count: 11
DOI: 10.2174/1570180811666140724184806
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science