(+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one | 860791-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one
• 英文别名: (+/-)-6-(1-naphthyl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one；6-naphthalen-1-ylpyrrolo[2,1-d][1,5]benzothiazepin-7-one
• CAS: 860791-99-7
• 化学式: C₂₂H₁₅NOS
• 分子量: 341.433
• InChiKey: GSHOISGQYADNHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one 、 二甲氨基甲酰氯 在 potassium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以77%的产率得到7-((Dimethylcarbamoyl)oxy)-6-(1-naphthyl)pyrrolo[2,1-d][1,5]benzothiazepine
  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：

  Alpha-溴代-1-萘乙酸乙酯 在 sodium hydroxide 、 五氯化磷 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one
  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

文献信息

• Apoptosis-inducing compounds
  申请人：The Universita'di Siena

  公开号：US06806267B1

  公开（公告）日：2004-10-19

  The present invention relates to pyrrolobenzoxazepines, pyrrolobenzthiazepines and related compounds having the ability to induce apoptosis, to pharmaceutical compositions comprising these compounds and to their use as anti-tumour agents.

  本发明涉及能够诱导细胞凋亡的吡咯并苯并噁唑、吡咯并苯并噻唑及相关化合物，以及包含这些化合物的药物组合物，以及它们作为抗肿瘤剂的用途。
• US6806267B1
  申请人：——

  公开号：US6806267B1

  公开（公告）日：2004-10-19
• 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
  作者：Margaret M. Mc Gee、Sandra Gemma、Stefania Butini、Anna Ramunno、Daniela M. Zisterer、Caterina Fattorusso、Bruno Catalanotti、Gagan Kukreja、Isabella Fiorini、Claudio Pisano、Carla Cucco、Ettore Novellino、Vito Nacci、D. Clive Williams、Giuseppe Campiani

  DOI：10.1021/jm049402y

  日期：2005.6.1

  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.