ALK inhibitors of bis-ortho-alkoxy-para-piperazinesubstituted-pyrimidines and -triazines for cancer treatment
Archives of pharmacal research, 2014•Springer
Syntheses of various bis-ortho-alkoxy-para-piperazineanilino-pyrimidines and-triazines of
KRCA-0008 analogs are described and their structure–activity-relationship to anaplastic
lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2, 4-pyrimidine analog (2) seems to
be most potent in both biochemical and cellular assay in this study, however it shows inferior
mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4, 6-
disubstituted pyrimidine and 2, 4-disubstituted triazine derivatives of KRCA-0008 are less …
KRCA-0008 analogs are described and their structure–activity-relationship to anaplastic
lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2, 4-pyrimidine analog (2) seems to
be most potent in both biochemical and cellular assay in this study, however it shows inferior
mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4, 6-
disubstituted pyrimidine and 2, 4-disubstituted triazine derivatives of KRCA-0008 are less …
Abstract
Syntheses of various bis-ortho-alkoxy-para-piperazineanilino-pyrimidines and -triazines of KRCA-0008 analogs are described and their structure–activity-relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2,4-pyrimidine analog (2) seems to be most potent in both biochemical and cellular assay in this study, however it shows inferior mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less potent or inactive to ALK wt., and this observation is explained with their molecular modeling compared to KRCA-0008.
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