Symmetric 4,4′-(piperidin-4-ylidenemethylene)bisphenol derivatives as novel tunable estrogen receptor (ER) modulators

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• 作者：Manabu Sato ; Kiminori Ohta ; ^{k-ohta@tohoku-pharm.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Asako Kaise ; Sayaka Aoto ; Yasuyuki Endo
• 关键词：Estrogen receptor modulator ; Piperidine ; 2 ; 2 ; 6 ; 6-Tetramethylpiperidine ; McMurry coupling ; Hydrophobicity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：24
• 期：5
• 页码：1089-1094
• 全文大小：687 K

文摘

We designed and synthesized 4,4′-(piperidin-4-ylidenemethylene)bisphenol derivatives as novel tunable estrogen receptor (ER) modulators. The introduction of hydrophobic substituents on the nitrogen atom of the piperidine ring enhanced ERα binding affinity. In addition, the introduction of four methyl groups adjacent to the piperidine ring nitrogen atom remarkably enhanced ERα binding affinity. N-Acetyl-2,2,6,6-tetramethylpiperidine derivative 3b showed high ERα binding affinity, high MCF-7 cell proliferation inducing activity, and high metabolic stability in rat liver S9 fractions.