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Symmetric 4,4'-(piperidin-4-ylidenemethylene)bisphenol derivatives as novel tunable estrogen receptor (ER) modulators
Manabu Sato1, Kiminori Ohta1, Asako Kaise1
1Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Abstract:
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.
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