Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
J Med Chem. 2013 Jan 10;56(1):160-6. doi: 10.1021/jm3013757. Epub 2012 Dec 19.
Here, we report the systematic synthesis and characterization of simple phenols bearing a trialkyl(aryl)silyl or trialkyl(aryl)germyl functional group as a hydrophobic substituent. These silicon and germanium analogues exhibited higher hydrophobicity than the corresponding carbon analogues, with a difference in log P value of approximately 0.6, independent of the alkyl(aryl) species. Trimethylsilylphenol and trimethylgermylphenol exhibited smaller pK(a) values than the corresponding carbon analogue or unsubstituted phenol, indicating that trialkylsilyl and trialkylgermyl functional groups have a negative substituent constant (σ). The trialkylsilyl- and trialkylgermylphenols exhibited more potent estrogenic activity as compared with the carbon analogues. The substituent parameters and structure-activity relationship reported here may be helpful for drug discovery utilizing the heavier group 14 elements.
在这里，我们报告了一系列简单酚类化合物的系统合成和特性，这些化合物带有三烷基（芳基）硅基或三烷基（芳基）锗基官能团作为疏水性取代基。这些硅和锗类似物的疏水性比相应的碳类似物更高，其 log P 值的差异约为 0.6，与烷基（芳基）种类无关。三甲基硅基苯酚和三甲基锗基苯酚的 pK(a)值小于相应的碳类似物或未取代的苯酚，表明三烷基硅基和三烷基锗基官能团具有负取代常数（σ）。与碳类似物相比，三烷基硅基-和三烷基锗基苯酚表现出更强的雌激素活性。这里报道的取代基参数和构效关系可能有助于利用较重的第 14 族元素进行药物发现。
