6-(t-butyl-dimethylsilyloxy)-2,5,7,8-tetramethyl-chroman-2-carboxylic acid methyl ester | 1187946-12-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-(t-butyl-dimethylsilyloxy)-2,5,7,8-tetramethyl-chroman-2-carboxylic acid methyl ester
• 英文别名: methyl (2R)-6-[tert-butyl(dimethyl)silyl]oxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxylate
• CAS: 1187946-12-8
• 化学式: C₂₁H₃₄O₄Si
• 分子量: 378.584
• InChiKey: RKGBSMGJYYMCOQ-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(t-butyl-dimethylsilyloxy)-2,5,7,8-tetramethyl-chroman-2-carboxylic acid methyl ester 在 二异丁基氢化铝 作用下， 以 正己烷 为溶剂， 反应 1.5h， 以88%的产率得到6-(t-butyldimethyl-silyloxy)-2,5,7,8-tetramethyl-chroman-2-carbaldehyde
  参考文献：
  名称：

  α-Tocopheryl Succinate as a Scaffold to Develop Potent Inhibitors of Breast Cancer Cell Adhesion

  摘要：

  This study is aimed at the pharmacological exploitation of a-tocopheryl succinate (1) to develop potent antiadhesion agents. Considering the structural cooperativity between the phytyl chain and the carboxylic terminus in determining the antiadhesion activity, our structural optimization led to compound 5 ([2-(4,8-dimethyl-non-1-enyl)-2,5,7,8-tetramethyl-chroman-6-yloxy]-acetic acid), which exhibited an-order-of-magnitude higher potency than I in blocking the adhesion of 4T1 metastatic breast cancer cells to extracellular matrix proteins (IC50, 0.6 mu M versus 10 mu M). Evidence indicates that the ability of compound 5 to block cell adhesion and migration was attributable to its effect on disrupting focal adhesion and actin cytoskeletal integrity by facilitating the degradation of focal adhesion kinase. Interactions between tumor cells and the ECM in the tumor microenvironment have been increasingly recognized as critical modulators of the metastatic potential of tumor cells. Consequently, the ability of compound 5 to block such interactions provides a unique pharmacological tool to shed light onto mechanisms that govern cell adhesion and tumor metastasis.

  DOI：

  10.1021/jm9002457
• 作为产物：
  描述：

  methyl (R)-(+)-3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carboxylate 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以99%的产率得到6-(t-butyl-dimethylsilyloxy)-2,5,7,8-tetramethyl-chroman-2-carboxylic acid methyl ester
  参考文献：
  名称：

  α-Tocopheryl Succinate as a Scaffold to Develop Potent Inhibitors of Breast Cancer Cell Adhesion

  摘要：

  This study is aimed at the pharmacological exploitation of a-tocopheryl succinate (1) to develop potent antiadhesion agents. Considering the structural cooperativity between the phytyl chain and the carboxylic terminus in determining the antiadhesion activity, our structural optimization led to compound 5 ([2-(4,8-dimethyl-non-1-enyl)-2,5,7,8-tetramethyl-chroman-6-yloxy]-acetic acid), which exhibited an-order-of-magnitude higher potency than I in blocking the adhesion of 4T1 metastatic breast cancer cells to extracellular matrix proteins (IC50, 0.6 mu M versus 10 mu M). Evidence indicates that the ability of compound 5 to block cell adhesion and migration was attributable to its effect on disrupting focal adhesion and actin cytoskeletal integrity by facilitating the degradation of focal adhesion kinase. Interactions between tumor cells and the ECM in the tumor microenvironment have been increasingly recognized as critical modulators of the metastatic potential of tumor cells. Consequently, the ability of compound 5 to block such interactions provides a unique pharmacological tool to shed light onto mechanisms that govern cell adhesion and tumor metastasis.

  DOI：

  10.1021/jm9002457

文献信息

• α-Tocopheryl Succinate as a Scaffold to Develop Potent Inhibitors of Breast Cancer Cell Adhesion
  作者：Dasheng Wang、Hsiao-Ching Chuang、Shu-Chuan Weng、Po-Hsien Huang、Hao-Yu Hsieh、Samuel K. Kulp、Ching-Shih Chen

  DOI：10.1021/jm9002457

  日期：2009.9.24

  This study is aimed at the pharmacological exploitation of a-tocopheryl succinate (1) to develop potent antiadhesion agents. Considering the structural cooperativity between the phytyl chain and the carboxylic terminus in determining the antiadhesion activity, our structural optimization led to compound 5 ([2-(4,8-dimethyl-non-1-enyl)-2,5,7,8-tetramethyl-chroman-6-yloxy]-acetic acid), which exhibited an-order-of-magnitude higher potency than I in blocking the adhesion of 4T1 metastatic breast cancer cells to extracellular matrix proteins (IC50, 0.6 mu M versus 10 mu M). Evidence indicates that the ability of compound 5 to block cell adhesion and migration was attributable to its effect on disrupting focal adhesion and actin cytoskeletal integrity by facilitating the degradation of focal adhesion kinase. Interactions between tumor cells and the ECM in the tumor microenvironment have been increasingly recognized as critical modulators of the metastatic potential of tumor cells. Consequently, the ability of compound 5 to block such interactions provides a unique pharmacological tool to shed light onto mechanisms that govern cell adhesion and tumor metastasis.