(6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methyl trifluoromethanesulfonate | 906357-45-7

• 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-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methyl trifluoromethanesulfonate
• 英文别名: (2,5,7,8-Tetramethyl-6-prop-2-enoxy-3,4-dihydrochromen-2-yl)methyl trifluoromethanesulfonate
• CAS: 906357-45-7
• 化学式: C₁₈H₂₃F₃O₅S
• 分子量: 408.439
• InChiKey: OSSJGJCZSVLRQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methyl trifluoromethanesulfonate 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 TG-55
  参考文献：
  名称：

  Development of Small-Molecule Cyclin D1-Ablative Agents

  摘要：

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.

  DOI：

  10.1021/jm060057h
• 作为产物：
  描述：

  奎诺二甲基丙烯酸酯 在 吡啶 、 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 54.5h， 生成 (6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methyl trifluoromethanesulfonate
  参考文献：
  名称：

  Development of Small-Molecule Cyclin D1-Ablative Agents

  摘要：

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.

  DOI：

  10.1021/jm060057h

文献信息

• Development of Small-Molecule Cyclin D1-Ablative Agents
  作者：Jui-Wen Huang、Chung-Wai Shiau、Jian Yang、Da-Sheng Wang、Hao-Chieh Chiu、Ching-Yu Chen、Ching-Shih Chen

  DOI：10.1021/jm060057h

  日期：2006.7.1

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.