7-((Dimethylcarbamoyl)oxy)-6-(1-naphthyl)pyrrolo[2,1-d][1,5]benzothiazepine

• 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: 7-((Dimethylcarbamoyl)oxy)-6-(1-naphthyl)pyrrolo[2,1-d][1,5]benzothiazepine
• 英文别名: 7-[(Dimethylcarbamoyl)oxy]-6-(1-naphthyl)pyrrolo[2,1-d][1,5]benzothiazepine；(6-naphthalen-1-ylpyrrolo[2,1-d][1,5]benzothiazepin-7-yl) N,N-dimethylcarbamate
• 化学式: C₂₅H₂₀N₂O₂S
• 分子量: 412.512
• InChiKey: TXTOTQCLFFCWAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Alpha-溴代-1-萘乙酸乙酯 在 sodium hydroxide 、 五氯化磷 、 potassium hydride 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 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

文献信息

• [EN] APOPTOSIS-INDUCING COMPOUNDS<br/>[FR] COMPOSES INDUISANT L'APOPTOSE
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2001058904A1

  公开（公告）日：2001-08-16

  The invention relates to a pharmaceutical composition comprising an apoptosis-inducing amount of a compound having general formula (I), wherein: (i) R1 represents an unsubstituted C6 or C10 aryl group; or a C6 aryl group substituted with Me or OMe; (ii) A represents O, S or S partially oxidized to sulfoxide; (iii) the cyclic group labelled F represents an unsubstituted C6 or C10 aryl-fused group or a C5 heteroaryl-fused group (nitrogen as heteroatom) or a benzo-fused system substituted with ethoxycarbonyl function; (iv) and Y represents the group (A) wherein R2 and R3 are independently hydrogen; or methyl; or Y represents the group CH3 or a (CH2)2CH3 group; or an unsubstituted C5 heteroaryl group (nitrogen as heteroatom). The compositions may be used for the treatment of tumours or other cancerous conditions, such as CML (chronic myeloid leukaemia), AML, in AIDS-related lymphomas (such as Karpowski's sarcoma, a sub-cutaneous lymphoma) and used as apoptotic agents in the treatment of cancers generally.

  本发明涉及一种药物组合物，包含一定量的通式（I）化合物，其诱导细胞凋亡的作用，其中：（i）R1代表未取代的C6或C10芳基；或取代有Me或OMe的C6芳基；（ii）A代表O，S或部分氧化为亚砜的S；（iii）标记为F的环状基团代表未取代的C6或C10芳基融合基团或取代有乙氧羰基的苯融合系统或C5杂环芳基融合基团（杂原子为氮）；（iv）Y代表基团（A），其中R2和R3独立地代表氢；或甲基；或Y代表基团CH3或（CH2）2CH3基团；或未取代的C5杂环芳基（杂原子为氮）。该组合物可用于治疗肿瘤或其他癌症疾病，如慢性髓性白血病（CML）、急性髓性白血病（AML）、艾滋病相关淋巴瘤（如卡波夫斯基肉瘤，一种皮下淋巴瘤）并可作为凋亡剂用于治疗各种癌症。
• 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。
• APOPTOSIS-INDUCING COMPOUNDS
  申请人：THE PROVOST, FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

  公开号：EP1255758A1

  公开（公告）日：2002-11-13
• 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.