- Estrogenic activity of bis(4-hydroxyphenyl)methanes with cyclic hydrophobic structure
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Monoalkylated bis(4-hydroxyphenyl)methanes (e.g., 1) are reported to show weak binding affinity for estrogen receptor (ER). We hypothesized that introduction of appropriately located hydrophobic substituents in these compounds would increase the binding affinity. Indeed, we found that bis(4-hydroxyphenyl)methane bearing a 3,3-dimethylcyclohexyl group (7) shows potent ERα binding affinity, comparable to that of estradiol. Bulkier substituents could be introduced at the 3,3-position without decreasing the affinity. However, the position of the substituents was critical: the 4,4-dimethylcyclohexyl derivative (2) showed very weak binding affinity. The compounds with high ER-binding affinity showed predominantly agonistic activity, together with weak antagonistic activity at high concentration, in cell proliferation assay with human breast cancer cell line MCF-7. Further structure-function studies of these compounds and their derivatives might lead to the development of more selective and potent estrogen receptor modulators.
- Kojima, Tomohiro,Ogawa, Takumi,Kitao, Souichiro,Sato, Manabu,Oda, Akifumi,Ohta, Kiminori,Endo, Yasuyuki
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- Direct and Unified Access to Carbon Radicals from Aliphatic Alcohols by Cost-Efficient Titanium-Mediated Homolytic C?OH Bond Cleavage
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Low-valent Ti-mediated homolytic C?O bond cleavage offers unified access to carbon radicals from ubiquitous non-activated tertiary, secondary, and even primary alcohols. In contrast to the representative Ti reagents, which were ineffective for this purpos
- Suga, Takuya,Takahashi, Yuuki,Miki, Chinatsu,Ukaji, Yutaka
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