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

• New ceritinib analogs by extensive functionalization of the tail piperidine ring were synthesized.
• All compounds were evaluated in H2228 cell line.
• Compound 9 exhibited robust tumor growth inhibition in vitro and vivo.

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.

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