N-{1,4-dioxo-3-[(pyridin-3-ylmethyl)amino]-1,4-dihydronaphthalen-2-yl}-N-(2-methoxyethyl)acetamide | 355404-70-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-{1,4-dioxo-3-[(pyridin-3-ylmethyl)amino]-1,4-dihydronaphthalen-2-yl}-N-(2-methoxyethyl)acetamide
• 英文别名: N-(2-methoxyethyl)-N-[3-(3-pyridylmethyl)amino-1,4-dihydro-1,4-dioxo-2-naphthalenyl]acetamide；N-(2-methoxyethyl)-N-[3-(pyridin-3-ylmethyl)amino-1,4-dihydro-1,4-dioxo-2-naphthalenyl]acetamide；N-[1,4-dioxo-3-(pyridin-3-ylmethylamino)naphthalen-2-yl]-N-(2-methoxyethyl)acetamide
• CAS: 355404-70-5
• 化学式: C₂₁H₂₁N₃O₄
• 分子量: 379.415
• InChiKey: QZKSEWQZEAYGRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-{1,4-dioxo-3-[(pyridin-3-ylmethyl)amino]-1,4-dihydronaphthalen-2-yl}-N-(2-methoxyethyl)acetamide 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-[({3-[N-acetyl-N-(2-methoxyethyl)]amino-1,4-dihydro-1,4-dioxo-2-naphthalenyl}amino)methyl]pyridine 1-oxide
  参考文献：
  名称：

  Fused imidazolium derivatives

  摘要：

  这项发明涉及药物，特别是用于治疗癌症的新型融合咪唑基衍生物，以及其新型合成中间化合物。这些新型咪唑基衍生物与芳基或杂环芳基环融合，其特征在于1-和/或3-位置被取代为具有从羟基、烷基等取代基中选择的取代基，具有出色的抗肿瘤活性和低毒性，并且作为具有广泛安全边界的抗癌剂而有用。

  公开号：

  US20030114508A1
• 作为产物：
  描述：

  2-氯-3-((2-甲氧基乙基)氨基)萘-1,4-二酮 在 硫酸 作用下， 以 甲苯 为溶剂， 反应 5.5h， 生成 N-{1,4-dioxo-3-[(pyridin-3-ylmethyl)amino]-1,4-dihydronaphthalen-2-yl}-N-(2-methoxyethyl)acetamide
  参考文献：
  名称：

  Dioxonaphthoimidazolium 是具有 SOX2 抑制特性的强效和选择性流氓干细胞清除剂

  摘要：

  多能干细胞在再生医学方面具有独特的定位，但只有将其致瘤倾向与其多能特性脱钩，才能实现其临床潜力。使用小分子去除残留的未分化多能细胞，否则这些细胞会转化为畸胎瘤和畸胎瘤，与非药物方法相比具有几个优势。Dioxonapthoimidazolium YM155 是一种存活素抑制剂，可诱导未分化干细胞的选择性和强效细胞死亡。在此，对干细胞毒性的结构要求进行了研究，发现其与恶性细胞中细胞毒性所必需的结构要求密切相关。对醌和咪唑鎓部分的依赖性很大，但对环取代基的依赖性较小，主要用于微调活动。鉴定出几种有效的类似物，如 YM155，抑制干细胞中的 survivin 并降低 SOX2。SOX2 的减少会导致多能因子的不平衡，这可能会促使细胞分化，从而降低异常畸胎瘤形成的风险。由于 NF-κB p50 亚基的磷酸化也被抑制，磷酸化-p50、SOX2 和 survivin 之间的串扰可能暗示 NF-κB 信号

  DOI：

  10.1002/cmdc.201600262

文献信息

• FUSED IMIDAZOLIUM DERIVATIVES
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1256576A1

  公开（公告）日：2002-11-13

  This invention relates to medicaments, particularly novel fused imidazolium derivatives useful for the treatment of cancers and novel synthetic intermediate compounds thereof. The novel imidazolium derivatives fused with an aryl or heteroaryl ring, characterized in that the 1- and/or 3-position is substituted by an alkyl group etc. having a substituent selected from the group consisting of -ORa, -SRa and the like, have excellent anti-tumor activity and low toxicity and are useful as anticancer agents having wide margins of safety.

  本发明涉及药物，特别是用于治疗癌症的新型融合咪唑鎓衍生物及其新型合成中间体化合物。 与芳基或杂芳基环融合的新型咪唑鎓衍生物，其特征在于1位和/或3位被烷基等取代，该烷基的取代基选自-ORa、-SRa等组成的组，具有优异的抗肿瘤活性和低毒性，可用作抗癌剂，具有较宽的安全范围。
• Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study
  作者：Si-Han Sherman Ho、Mei-Yi Sim、Wei-Loong Sherman Yee、Tianming Yang、Shyi-Peng John Yuen、Mei-Lin Go

  DOI：10.1016/j.ejmech.2015.09.026

  日期：2015.11

  The anticancer agent YM155 is widely investigated as a specific survivin suppressant. More recently, YM155 was found to induce DNA damage and this has raised doubts as to whether survivin is its primary target. In an effort to assess the contribution of DNA damage to the anticancer activity of YM155, several analogs were prepared and evaluated for antiproliferative activity on malignant cells, participation in DNA intercalation and free radical generation by redox cycling. The intact positively charged scaffold was found to be essential for antiproliferative activity and intercalation but was less critical for redox cycling where the minimal requirement was a pared down bicyclic quinone. Side chain requirements at the N-1 and N-3 positions of the scaffold were more alike for redox cycling and intercalation than antiproliferative activity, underscoring yet again, the limited structural overlaps for these activities. Furthermore, antiproliferative activities were poorly correlated to DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23 nM), exceeding that of YM155, was found for a minimally substituted methyl analog AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA intercalator but with weak redox cycling activity. Thus, the capacity of this scaffold to inflict direct DNA damage leading to cell death may not be significant and YM155 should not be routinely classified as a DNA damaging agent. (C) 2015 Elsevier Masson SAS. All rights reserved.
• US6734203B2
  申请人：——

  公开号：US6734203B2

  公开（公告）日：2004-05-11
• Fused imidazolium derivatives
  申请人：——

  公开号：US20030114508A1

  公开（公告）日：2003-06-19

  This invention relates to medicaments, particularly novel fused imidazolium derivatives useful for the treatment of cancers and novel synthetic intermediate compounds thereof. The novel imidazolium derivatives fused with an aryl or heteroaryl ring, characterized in that the 1- and/or 3-position is substituted by an alkyl group etc. having a substituent selected from the group consisting of —OR a , —SRa and the like, have excellent anti-tumor activity and low toxicity and are useful as anticancer agents having wide margins of safety. 1

  这项发明涉及药物，特别是用于治疗癌症的新型融合咪唑基衍生物，以及其新型合成中间化合物。这些新型咪唑基衍生物与芳基或杂环芳基环融合，其特征在于1-和/或3-位置被取代为具有从羟基、烷基等取代基中选择的取代基，具有出色的抗肿瘤活性和低毒性，并且作为具有广泛安全边界的抗癌剂而有用。
• Dioxonaphthoimidazoliums are Potent and Selective Rogue Stem Cell Clearing Agents with SOX2-Suppressing Properties
  作者：Si-Han Sherman Ho、Azhar Ali、Yi-Cheng Ng、Kuen-Kuen Millie Lam、Shu Wang、Woon-Khiong Chan、Tan-Min Chin、Mei-Lin Go

  DOI：10.1002/cmdc.201600262

  日期：2016.9.6

  non‐pharmacological methods. Dioxonapthoimidazolium YM155, a survivin suppressant, induced selective and potent cell death of undifferentiated stem cells. Herein, the structural requirements for stemotoxicity were investigated and found to be closely aligned with those essential for cytotoxicity in malignant cells. There was a critical reliance on the quinone and imidazolium moieties but a lesser dependence on

  多能干细胞在再生医学方面具有独特的定位，但只有将其致瘤倾向与其多能特性脱钩，才能实现其临床潜力。使用小分子去除残留的未分化多能细胞，否则这些细胞会转化为畸胎瘤和畸胎瘤，与非药物方法相比具有几个优势。Dioxonapthoimidazolium YM155 是一种存活素抑制剂，可诱导未分化干细胞的选择性和强效细胞死亡。在此，对干细胞毒性的结构要求进行了研究，发现其与恶性细胞中细胞毒性所必需的结构要求密切相关。对醌和咪唑鎓部分的依赖性很大，但对环取代基的依赖性较小，主要用于微调活动。鉴定出几种有效的类似物，如 YM155，抑制干细胞中的 survivin 并降低 SOX2。SOX2 的减少会导致多能因子的不平衡，这可能会促使细胞分化，从而降低异常畸胎瘤形成的风险。由于 NF-κB p50 亚基的磷酸化也被抑制，磷酸化-p50、SOX2 和 survivin 之间的串扰可能暗示 NF-κB 信号