N-(1,4-dioxo-3-((2-methoxyethyl)amino)-1,4-dihydronaphthalen-2-yl)acetamide | 354824-11-6

• 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-((2-methoxyethyl)amino)-1,4-dihydronaphthalen-2-yl)acetamide
• 英文别名: N-[3-(2-methoxyethyl)amino-1,4-dihydro-1,4-dioxo-2-naphthalenyl]acetamide；N-[3-(2-methoxyethylamino)-1,4-dioxonaphthalen-2-yl]acetamide
• CAS: 354824-11-6
• 化学式: C₁₅H₁₆N₂O₄
• 分子量: 288.303
• InChiKey: HABKMYLFAPUVFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1,4-dioxo-3-((2-methoxyethyl)amino)-1,4-dihydronaphthalen-2-yl)acetamide 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 1-(2-methoxyethyl)-2-methyl-1H-naphtho[2,3-d]imidazole-4,9-dione
  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-氨基-3-氯-1,4-萘醌 在 硫酸 、 三乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 2.5h， 生成 N-(1,4-dioxo-3-((2-methoxyethyl)amino)-1,4-dihydronaphthalen-2-yl)acetamide
  参考文献：
  名称：

  Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.09.026

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。
• US6734203B2
  申请人：——

  公开号：US6734203B2

  公开（公告）日：2004-05-11
• 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.
• 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。