(+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one-3-carboxylic acid | 860792-01-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one-3-carboxylic acid
• 英文别名: 6-Naphthalen-1-yl-7-oxopyrrolo[2,1-d][1,5]benzoxazepine-3-carboxylic acid
• CAS: 860792-01-4
• 化学式: C₂₃H₁₅NO₄
• 分子量: 369.376
• InChiKey: HVOLCGGOOLEICO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one-3-carboxylic acid 在 四(三苯基膦)钯 、 苯硅烷 、 potassium hydride 、 cesium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 7-(Dimethylcarbamoyloxy)-6-naphthalen-1-ylpyrrolo[2,1-d][1,5]benzoxazepine-3-carboxylic acid
  参考文献：
  名称：

  Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target

  摘要：

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.

  DOI：

  10.1021/jm049402y
• 作为产物：
  描述：

  4-氨基-3-羟基苯甲酸 在 吗啉 、 sodium hydroxide 、 四(三苯基膦)钯 、 五氯化磷 、 sodium hydride 、 溶剂黄146 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one-3-carboxylic acid
  参考文献：
  名称：

  Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target

  摘要：

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.

  DOI：

  10.1021/jm049402y