1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as Orally Bioavailable Transcriptional Function Suppressors of Estrogen-Related Receptor 伪

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• 作者：Shilin Xu ; Xiaoxi Zhuang ; Xiaofen Pan ; Zhang Zhang ; Lei Duan ; Yingxue Liu ; Lianwen Zhang ; Xiaomei Ren ; Ke Ding
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 13, 2013
• 年：2013
• 卷：56
• 期：11
• 页码：4631-4640
• 全文大小：502K
• 年卷期：v.56,no.11(June 13, 2013)
• ISSN：1520-4804

文摘

Estrogen-related receptor 伪 is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure鈥揳ctivity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2,3-triazoles as novel suppressors of ERR伪 transcriptional functions. The most promising compound, 2-aminophenyl-(1-(3-isopropylphenyl)-1H-1,2,3-triazol-4-yl)methanone (14n), potently suppressed the transcriptional functions of ERR伪 with IC₅₀ = 0.021 渭M in a cell-based reporter gene assay and also decreased both the mRNA levels and the protein levels of ERR伪 and the downstream targets. This compound inhibited the proliferation and migration of breast cancer cells with high level of ERR伪. Preliminary pharmacokinetic studies suggested that it possessed a good pharmacokinetic profile with an oral bioavailability of 71.8%. The compounds may serve as novel small molecule probes for further validation of ERR伪 as a molecular target for anticancer drug development.