Design, synthesis and evaluation of novel diaryl urea derivatives as potential antitumor agents

Eur J Med Chem. 2014 Apr 22:77:351-60. doi: 10.1016/j.ejmech.2014.03.020.

Chenshu Lu ¹, Ke Tang ¹, Yan Li ¹, Peng Li ¹, Ziyun Lin ¹, Dali Yin ¹, Xiaoguang Chen ², Haihong Huang ³

Affiliations

1 Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
2 Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: chxg@imm.ac.cn.
3 Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address: joyce@imm.ac.cn.

PMID: 24675135 DOI: 10.1016/j.ejmech.2014.03.020

Abstract

A novel series of diaryl ureas containing different linker groups were designed and synthesized. Their in vitro antitumor activity against MX-1, A375, HepG2, Ketr3 and HT-29 was evaluated using the standard MTT assay. Compounds having a rigid linker group such as vinyl, ethynyl and phenyl showed significant inhibitory activity against a variety of Cancer cell lines. Specifically, compound 23 with a phenyl linker group demonstrated broad-spectrum antitumor activity with IC50 values of 5.17-6.46 μM against five tested tumor cell lines. Compound 23 is more potent than reference drug sorafenib (8.27-15.2 μM), representing a promising lead for further optimization.

Keywords

Antitumor activity; Diaryl ureas; Linker; Sorafenib.

Name
Email *

	Sorry, but the email address you supplied was invalid.