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Design, synthesis, and biological evaluation of 2-(5-methyl-1H-pyrazol-1-yl) acetamide derivatives as androgen receptor antagonists
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Shandong, PR China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Shandong, PR China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Shandong, PR China.
Örebro University, School of Science and Technology. Biology, The Life Science Center.
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2019 (English)In: Medicinal Chemistry Research, ISSN 1054-2523, E-ISSN 1554-8120, Vol. 28, no 3, p. 380-386Article in journal (Refereed) Published
Abstract [en]

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=35.0M), especially 6g with IC50 value of 13.6 mu M.

Place, publisher, year, edition, pages
Springer, 2019. Vol. 28, no 3, p. 380-386
Keywords [en]
Androgen receptor, Prostate cancer, Antagonists, Pyrazole derivatives
National Category
Pharmacology and Toxicology Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-73118DOI: 10.1007/s00044-019-02291-yISI: 000459449600013Scopus ID: 2-s2.0-85060553900OAI: oai:DiVA.org:oru-73118DiVA, id: diva2:1296203
Funder
Knowledge Foundation, 201550084
Note

Funding Agencies:

National Natural Science Foundation of China  21272140 

Key Research and Development Project of Shandong Province  2017CXGC1401 

Available from: 2019-03-14 Created: 2019-03-14 Last updated: 2019-03-14Bibliographically approved

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Asnake, SolomonOlsson, Per-Erik

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