2. Academic Validation
  3. Design, Synthesis, and Biological Evaluation of 3-Amino-pyrazine-2-carboxamide Derivatives as Novel FGFR Inhibitors

Design, Synthesis, and Biological Evaluation of 3-Amino-pyrazine-2-carboxamide Derivatives as Novel FGFR Inhibitors

  • ACS Med Chem Lett. 2024 Nov 5;15(11):2019-2031. doi: 10.1021/acsmedchemlett.4c00431.
Jia Zheng 1,  Wei Zhang 2,  Dan Ni 1,  Shuang Zhao 1,  Yi He 1,  Junchi Hu 1,  Linfeng Li 2,  Yongjun Dang 1,  Zufeng Guo 2,  Shenyou Nie 1
Affiliations

Affiliations

  • 1 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), College of Pharmacy and Department of Urology of the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
  • 2 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), College of Pharmacy and Department of Breast and Thyroid Surgery of the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
PMID: 39563808 DOI: 10.1021/acsmedchemlett.4c00431
Abstract

FGFR has been considered a crucial oncogenic driver and promising target for Cancer therapy. Herein, we reported the design and synthesis of 3-amino-N-(3,5-dihydroxyphenyl)-6-methylpyrazine-2-carboxamide derivatives as novel FGFR inhibitors. SAR exploration led to the identification of 18i as a pan-FGFR inhibitor with favorable in vitro activity against FGFR1-4. Moreover, 18i blocked the activation of FGFR and downstream signaling pathways at the submicromolar level and exhibited potent antitumor activity in multiple Cancer cell lines with FGFR abnormalities. Molecular docking was performed to investigate the possible binding modes of 18i within the binding site of FGFR2. These results suggest that compound 18i is a promising candidate for further drug discovery.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-168653
    FGFR抑制剂
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