4-[(6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzaldehyde | 906357-46-8

• 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: 4-[(6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzaldehyde
• 英文别名: 4-[(2,5,7,8-Tetramethyl-6-prop-2-enoxy-3,4-dihydrochromen-2-yl)methoxy]benzaldehyde
• CAS: 906357-46-8
• 化学式: C₂₄H₂₈O₄
• 分子量: 380.484
• InChiKey: ONSFOWTWJHXELQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  4-[(6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzaldehyde 、 2,4-噻唑烷二酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以71%的产率得到5-[4-(6-allyloxy-2,5,7,8-tetramethylchroman-2-ylmethoxy)benzylidene]-2,4-thiazolidinedione
  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 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 55.0h， 生成 4-[(6-allyloxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzaldehyde
  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