Synthesis and anticancer activities of ceritinib analogs modified in the terminal piperidine ring

Eur J Med Chem. 2015 Mar 26:93:1-8. doi: 10.1016/j.ejmech.2015.01.056.

Peng Wang ¹, Jin Cai ², Junqing Chen ², Min Ji ³

Affiliations

1 Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China; School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: wangpeng159seu@hotmail.com.
2 School of Chemistry & Chemical Engineering, Southeast University, Nanjing 210096, China.
3 School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: jimin@seu.edu.cn.

PMID: 25644671 DOI: 10.1016/j.ejmech.2015.01.056

Abstract

A series of new ceritinib analogs by extensive functionalization of the tail piperidine ring with various phosphamides and carbamates have been synthesized. All the ceritinib derivatives were evaluated for their cytotoxic activities against H2228 cell line. From the activity profile obtained, three of the tested compounds (compounds 4, 7 and 9) showed significant cytotoxic effects. Among these derivatives compound 9 was found to possess cytotoxicity that is better than standard drug ceritinib (IC50 = 24 nM). Moreover, compound 9 demonstrated robust tumor growth inhibition in vivo model.

Keywords

ALK; Anticancer; Ceritinib analogs; Synthesis.

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