(+/-)-α-[[2-(1H-pyrrol-1-yl)phenyl]oxy]naphth-1-ylacetic acid ethyl ester | 354759-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (+/-)-α-[[2-(1H-pyrrol-1-yl)phenyl]oxy]naphth-1-ylacetic acid ethyl ester
• 英文别名: (+/-)-α-[[2-(1H-Pyrrol-1-yl)phenyl]oxy]-(1-naphthyl)acetic Acid Ethyl Ester；α-[[2-(1H-Pyrrol-1-yl)phenyl]oxy]-(1-naphthyl)acetic Acid Ethyl Ester；(+/-)-alpha-[[2-(1H-Pyrrol-1-yl)phenyl]oxy]-(1-naphthyl)acetic Acid Ethyl Ester；ethyl 2-naphthalen-1-yl-2-(2-pyrrol-1-ylphenoxy)acetate
• CAS: 354759-04-9
• 化学式: C₂₄H₂₁NO₃
• 分子量: 371.436
• InChiKey: RXSULXWYAUHIAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  40.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-α-[[2-(1H-pyrrol-1-yl)phenyl]oxy]naphth-1-ylacetic acid ethyl ester 在 sodium hydroxide 、 五氯化磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 (+/-)-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-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
• 作为产物：
  描述：

  2-(1H-吡咯-1-基)苯醇 、 Alpha-溴代-1-萘乙酸乙酯 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (+/-)-α-[[2-(1H-pyrrol-1-yl)phenyl]oxy]naphth-1-ylacetic acid ethyl ester
  参考文献：
  名称：

  Apoptosis-inducing compounds

  摘要：

  本发明涉及能够诱导细胞凋亡的吡咯苯并噁唑环烯和吡咯苯并噻唑环烯以及相关化合物，涉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。

  公开号：

  US06806267B1

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苯并噁唑环烯和吡咯苯并噻唑环烯以及相关化合物，涉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
• [EN] APOPTOSIS-INDUCING COMPOUNDS<br/>[FR] COMPOSES INDUISANT L'APOPTOSE
  申请人：——

  公开号：WO2001058904A9

  公开（公告）日：2002-02-21

  [EN] 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.
  [FR] L'invention concerne une composition pharmaceutique comprenant une quantité induisant l'apoptose d'un composé représenté par la formule générale (I), dans laquelle: (i) R1 représente un groupe aryle en C6 ou C10 non substitué ou un groupe aryle en C6 substitué par Me ou OMe; (ii) A représente O, S ou S partiellement oxydé en sulfoxyde; (iii) le groupe cyclique appelé F représente un groupe aryl-condensé en C6 ou C10 non substitué ou un groupe hétéroaryl-condensé en C5 (avec l'azote comme hétéroatome) ou un système benzo-condensé substitué par une fonction éthoxycarbonyle; (iv) et Y représente le groupe (A) où R2 et R3 désignent indépendamment hydrogène, ou méthyle; ou Y représente le groupe CH3 ou un groupe (CH2)2CH3, ou un groupe hétéroaryle en C5 non susbtitué (avec l'azote comme hétéroatome). Les compositions selon l'invention peuvent être utilisées d'une part, pour le traitement des tumeurs ou autres états cancéreux, notamment la leucémie myéloïde chronique, la LAM et les lymphomes liés au SIDA (tels que le sarcome de Karpowski, le lymphome sous-cutané) et d'autre part, comme agents apoptotiques dans le traitement des cancers de manière générale.
• 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.