Design, synthesis, and biological evaluation of 2-(5-methyl-1H-pyrazol-1-yl) acetamide derivatives as androgen receptor antagonists
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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.
KeywordsAndrogen receptor Prostate cancer Antagonists Pyrazole derivatives
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.
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Conflict of interest
The authors declare that they have no conflict of interest.
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