Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents

Jee Sun Yang, Chun Ho Park, Chulho Lee, Hwan Kim, Changmok Oh, Yejoo Choi, Jong Soon Kang, Jieun Yun, Jin Hyun Jeong, Myung Hwa Kim, Gyoonhee Han

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23 Citations (Scopus)


The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML. A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 2014 Oct 6

Bibliographical note

Funding Information:
This research was supported by a grant from the Translational Research Center for Protein Function Control ( NRF-2009-0083522 ), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( NRF-2013R1A1A2008165 ), Ministry of Health & Welfare ( A120478 ), and the Ministry of Science, ICT & Future Planning ( NRF-2013M3A6A4072536 ).

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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