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Design, synthesis, and biological evaluation of 2-(5-methyl-1H-pyrazol-1-yl) acetamide derivatives as androgen receptor antagonists

  • Junze Dong
  • Jingya Zhang
  • Zilu Li
  • Solomon Asnake
  • Daoguang Zhang
  • Per-Erik Olsson
  • Guisen ZhaoEmail author
Original Research
  • 16 Downloads

Abstract

Androgen receptor (AR) signaling is often activated in prostate cancer (PCa) cells, and blockage of this signaling by AR antagonists is an important strategy in PCa therapy. In this study, we designed and synthesized a series of 2-(5-methyl-1H-pyrazol-1-yl) acetamide derivatives, and evaluated their biological activities. AR luciferase reporter assay revealed compound 6f (59.7%) as a potent AR antagonist. Some compounds in this series showed higher anti-proliferative activity against LNCaP cells than Bicalutamide (IC50 = 35.0 μM), especially 6g with IC50 value of 13.6 μM.

Keywords

Androgen receptor Prostate cancer Antagonists Pyrazole derivatives 

Notes

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 21272140), Key Research and Development Project of Shandong Province (No. 2017CXGC1401), and the Knowledge Foundation (No. 201550084) of Sweden.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2291_MOESM1_ESM.docx (3.5 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Junze Dong
    • 1
  • Jingya Zhang
    • 1
  • Zilu Li
    • 1
  • Solomon Asnake
    • 2
  • Daoguang Zhang
    • 1
  • Per-Erik Olsson
    • 2
  • Guisen Zhao
    • 1
    Email author
  1. 1.Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical SciencesShandong UniversityJinanPR China
  2. 2.Biology, The Life Science Center, School of Science and TechnologyÖrebro UniversityÖrebroSweden

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