Synthesis of novel 1H-Pyrazolo[3,4-b]pyridine derivatives as DYRK 1A/1B inhibitors

Areum Park, Jieon Hwang, Joo Youn Lee, Eun Ji Heo, Yoon Ju Na, Sein Kang, Kyu Sung Jeong, Ki Young Kim, Sang Joon Shin, Hyuk Lee

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8 Citations (Scopus)


As DYRK1A and 1B inhibitors, 1H-pyrazolo[3,4-b]pyridine derivatives were synthesized. Mostly, 3-aryl-5-arylamino compounds (6) and 3,5-diaryl compounds (8 and 9) were prepared and especially, 3,5-diaryl compound 8 and 9 showed excellent DYRK1B inhibitory enzymatic activities with IC50 Values of 3–287 nM. Among them, 3-(4-hydroxyphenyl), 5-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridine (8h) exhibited the highest inhibitory enzymatic activity (IC50 = 3 nM) and cell proliferation inhibitory activity (IC50 = 1.6 µM) towards HCT116 colon cancer cells. Also compound 8h has excellent inhibitory activities in patient-derived colon cancer organoids model as well as in 3D spheroid assay model of SW480 and SW620. The docking study supported that we confirmed that compound 8h binds to DYRK1B through various hydrogen bonding interactions and hydrophobic interactions.

Original languageEnglish
Article number128226
JournalBioorganic and Medicinal Chemistry Letters
Publication statusPublished - 2021 Sept 1

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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