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

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• 作者：Hyeon Ji Lee ; Muhammad Latif ; Hyeonjeong Choe ; Imran Ali…
• 关键词：ALK ; Kinases ; Diaminopyrimidine ; Diaminotriazine ; Inhibitors
• 刊名：Archives of Pharmacal Research
• 出版年：2014
• 出版时间：September 2014
• 年：2014
• 卷：37
• 期：9
• 页码：1130-1138
• 全文大小：708 KB
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• 作者单位：Hyeon Ji Lee (1) (2)
  Muhammad Latif (1) (3) (4)
  Hyeonjeong Choe (1) (3)
  Imran Ali (1) (3)
  Heung Kyoung Lee (1)
  Eun Hye Yang (1)
  Jeong In Yun (1) (5)
  Chong Hak Chae (1) (4)
  Jae-Kyung Jung (2)
  Hyoung Rae Kim (1)
  Chong Ock Lee (1)
  Chi Hoon Park (1)
  Kwangho Lee (1) (3)
  
  1. Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Taejon, 305-600, Republic of Korea
  2. College of Pharmacy, Chungbuk National University, Ch’ongju, 361-763, Republic of Korea
  3. Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Taejon, 305-350, Republic of Korea
  4. Korea Chemical Bank, Taejon, 305-600, Republic of Korea
  5. College of Pharmacy, Chungnam National University, Taejon, 305-764, Republic of Korea
  
• ISSN：1976-3786

文摘

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.