4,4′-bis[2-(pyrrolidin-1-yl)ethoxy]phenyl ketone | 1472617-91-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4′-bis[2-(pyrrolidin-1-yl)ethoxy]phenyl ketone
• 英文别名: Bis[4-(2-pyrrolidin-1-ylethoxy)phenyl]methanone
• CAS: 1472617-91-6
• 化学式: C₂₅H₃₂N₂O₃
• 分子量: 408.541
• InChiKey: FQLJWAKZAGAITD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  42.01
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  正丁基锂 、 4,4′-bis[2-(pyrrolidin-1-yl)ethoxy]phenyl ketone 以 四氢呋喃 、 正己烷 为溶剂， 反应 17.5h， 以92%的产率得到
  参考文献：
  名称：

  Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen species-dependent signaling pathway

  摘要：

  Tamoxifen is an anticancer agent widely used for treatment of estrogen receptor (ER alpha)-positive breast cancer. We previously developed a novel synthesis of tamoxifen and its derivatives, named Ridaifens (RIDS). Some of them, including RID-SB8, exhibited a stronger anticancer activity than tamoxifen in ER alpha-positive MCF-7 cells while having lost the affinity for ER alpha, suggesting an ER alpha-independent anticancer mode of action. In this study, we investigated the underlying mechanism by which RID-SB8 exerts anticancer activity. As expected, anticancer activity of RID-SB8 was not influenced upon knockdown of ER alpha expression in MCF-7 cells. RID-SB8 exerted similar anticancer effects on thirteen ER alpha-negative cancer cell lines including human gliosarcoma SF539 cells. In SF539 cells, RID-SB8 triggered loss of mitochondrial membrane potential (Delta Psi(m)) and progression of apoptosis accompanied by activation of caspases and translocation of apoptosis-inducing factor (AIF) to the nucleus. Furthermore, it induced reactive oxygen species (ROS), and a ROS scavenger, N-acetylcysteine (NAC), canceled loss of Delta Psi(m) and progression of apoptosis triggered by RID-SB8. Using fifteen human cancer cell lines, we demonstrated a significant correlation between RID-SB8 concentration required for ROS production and that required for cytotoxic effect across these cell lines, but such correlation was not observed for tamoxifen. Finally, the selective induction of ROS and cytotoxic effect on cancer cells by RID-SB8 were confirmed. From these results, we concluded that RID-SB8 exerts an anticancer effect via a mode of action distinct from tamoxifen, and that RID-SB8 could become a promising anticancer lead compound which selectively induces ROS formation and apoptosis in cancer cells. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2013.08.020
• 作为产物：
  描述：

  4,4'-二羟基二苯甲酮 、 N-(2-氯乙基)吡咯烷盐酸盐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 paraffin oil 为溶剂， 反应 7.75h， 以85%的产率得到4,4′-bis[2-(pyrrolidin-1-yl)ethoxy]phenyl ketone
  参考文献：
  名称：

  Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen species-dependent signaling pathway

  摘要：

  Tamoxifen is an anticancer agent widely used for treatment of estrogen receptor (ER alpha)-positive breast cancer. We previously developed a novel synthesis of tamoxifen and its derivatives, named Ridaifens (RIDS). Some of them, including RID-SB8, exhibited a stronger anticancer activity than tamoxifen in ER alpha-positive MCF-7 cells while having lost the affinity for ER alpha, suggesting an ER alpha-independent anticancer mode of action. In this study, we investigated the underlying mechanism by which RID-SB8 exerts anticancer activity. As expected, anticancer activity of RID-SB8 was not influenced upon knockdown of ER alpha expression in MCF-7 cells. RID-SB8 exerted similar anticancer effects on thirteen ER alpha-negative cancer cell lines including human gliosarcoma SF539 cells. In SF539 cells, RID-SB8 triggered loss of mitochondrial membrane potential (Delta Psi(m)) and progression of apoptosis accompanied by activation of caspases and translocation of apoptosis-inducing factor (AIF) to the nucleus. Furthermore, it induced reactive oxygen species (ROS), and a ROS scavenger, N-acetylcysteine (NAC), canceled loss of Delta Psi(m) and progression of apoptosis triggered by RID-SB8. Using fifteen human cancer cell lines, we demonstrated a significant correlation between RID-SB8 concentration required for ROS production and that required for cytotoxic effect across these cell lines, but such correlation was not observed for tamoxifen. Finally, the selective induction of ROS and cytotoxic effect on cancer cells by RID-SB8 were confirmed. From these results, we concluded that RID-SB8 exerts an anticancer effect via a mode of action distinct from tamoxifen, and that RID-SB8 could become a promising anticancer lead compound which selectively induces ROS formation and apoptosis in cancer cells. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2013.08.020

文献信息

• [EN] ANTITHROMBOTIC DIAMINES<br/>[FR] DIAMINES ANTITHROMBOTIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1997025033A1

  公开（公告）日：1997-07-17

  (EN) This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of diamines of formula (I) as defined herein. It also provides novel compounds of formula (I), processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula (I).(FR) La présente invention concerne l'utilisation, comme inhibiteurs de thrombine, inhibiteurs de coagulation et agents destinés aux désordres de la thromboembolie, de diamines de formule I telle qu'elle est définie dans la description. L'invention concerne aussi des composés nouveaux de formule I, des procédés et des produits intermédiaires pour leur préparation, et des formulations pharmaceutiques comprenant les composés nouveaux de formule I.

  该应用涉及使用公式（I）所定义的二胺作为凝血酶抑制剂、凝血抑制剂和血栓栓塞疾病药物的用途。它还提供了公式（I）的新化合物、其制备过程和中间体，以及包含公式（I）的新药物配方。
• EP0863755A4
  申请人：——

  公开号：EP0863755A4

  公开（公告）日：1999-01-20
• ANTITHROMBOTIC DIAMINES
  申请人：ELI LILLY AND COMPANY

  公开号：EP0863755A1

  公开（公告）日：1998-09-16
• EP1027051A4
  申请人：——

  公开号：EP1027051A4

  公开（公告）日：2001-03-07
• ANTITHROMBOTIC AGENTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1027051A1

  公开（公告）日：2000-08-16