ALK inhibitors of bis-ortho-alkoxy-para-piperazinesubstituted-pyrimidines and -triazines for cancer treatment

作者：Lee Hyeon Ji; Latif Muhammad; Choe Hyeonjeong; Ali Imran; Lee Heung Kyoung; Yang Eun Hye; Yun Jeong In; Chae Chong Hak; Jung Jae Kyung; Kim Hyoung Rae; Lee Chong Ock; Park Chi Hoon; Lee Kwangho^*

来源：Archives of Pharmacal Research, 2014, 37(9): 1130-1138.

DOI：10.1007/s12272-013-0323-z

• ALK
• Kinases
• Diaminopyrimidine
• Diaminotriazine
• Inhibitors

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.

• 出版日期2014-9