N,N'-(9,10-dioxo-9,10-dihydroanthracene-2,6-diyl)bis(2-morpholinoacetamide) | 55077-08-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: N,N'-(9,10-dioxo-9,10-dihydroanthracene-2,6-diyl)bis(2-morpholinoacetamide)
• 英文别名: 2-Morpholin-4-yl-N-[6-(2-morpholin-4-yl-acetylamino)-9,10-dioxo-9,10-dihydro-anthracen-2-yl]-acetamide；2-morpholin-4-yl-N-[6-[(2-morpholin-4-ylacetyl)amino]-9,10-dioxoanthracen-2-yl]acetamide
• CAS: 55077-08-2
• 化学式: C₂₆H₂₈N₄O₆
• 分子量: 492.532
• InChiKey: RDUDGLRJNZMVNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氨基蒽醌 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 N,N'-(9,10-dioxo-9,10-dihydroanthracene-2,6-diyl)bis(2-morpholinoacetamide)
  参考文献：
  名称：

  破译新型双取代蒽醌衍生物与 G-四链体 DNA 的结合表现出选择性癌细胞细胞毒性

  摘要：

  基于蒽醌的化合物以其结合双链体和 G-四链体 DNA 的能力而闻名。研究此类化合物的成员如何特异性识别 G-四链体 DNA 而不是双链体 DNA 是一个重要的挑战。我们设计并合成了 10 种具有不同哌嗪基侧链的新型 2,6-二取代蒽醌衍生物。四链体和双链体 DNA 之间的结构差异用于探测这些衍生物与 G-四链体 DNA 结合的末端堆叠模式。发现这些配体会引发细胞凋亡，对癌细胞表现出比正常细胞更高的选择性细胞毒性。

  DOI：

  10.1002/cmdc.202200436

文献信息

• Anthracene-9,10-diones as potential anticancer agents. Synthesis, DNA-binding, and biological studies on a series of 2,6-disubstituted derivatives
  作者：Mavis Agbandje、Terence C. Jenkins、Robert McKenna、Anthony P. Reszka、Stephen Neidle

  DOI：10.1021/jm00086a010

  日期：1992.4

  A series of 2,6-bis(omega-aminoalkanamido)anthracene-9,10-diones (9,10-anthraquinones), of general formula Ar(NHCO(CH2)nNR2)2, where Ar = anthracene-9,10-dione and n = 1 or 2, have been synthesized by treatment of the corresponding bis(omega-haloalkanamido) derivatives with appropriate secondary amines. The DNA-binding properties of these compounds were evaluated by thermal denaturation studies, unwinding of closed-circular DNA, determination of association constants in solution, and examined by molecular modeling. A representative compound in the series has been examined by X-ray crystallography. In vitro cytotoxicity data is reported for the compounds and some indications of structure-activity relationships have been discerned. In particular, those compounds with two methylene links (n = 2) in each side chain separating the amide and terminal amine moieties have superior activity and, in general, enhanced DNA binding characteristics. It is postulated that the mode of reversible binding of these compounds to DNA involves the side chains occupying both major and minor grooves and, further, that this may confer cytotoxic properties which are distinct from those of previously reported anthracene-9,10-dione cytotoxins.
• INTERCALATING AGENTS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LTD.

  公开号：EP0482119A1

  公开（公告）日：1992-04-29
• [EN] INTERCALATING AGENTS
  申请人：CANCER RESEARCH TECHNOLOGY LTD.

  公开号：WO1991000265A1

  公开（公告）日：1991-01-10

  (EN) Compounds are disclosed having general formula (I), in which n is 1, 2 or 3; and R1 and R2 are each, independently, an ethyl, hydroxyethyl, or hydroxymethyl group; or R1 and R2, together with the nitrogen atom to which they are attached, form a cyclic group which is a 1-piperidino, 2- or 4-(2-hydroxyethyl)-1-piperidino, 2-hydroxymethyl-1-piperidino, 4-(2-hydroxyethyl)- or 4-methyl-1-piperazino, or 4-morpholino group; or a pharmaceutically acceptable salt thereof. The compounds have utility as anti-cancer agents. A method of preparing the compounds, and pharmaceutical compositions containing the compounds, are also disclosed.(FR) L'invention se rapporte à des composés représentés par la formule générale (I); où n est égal à 1, à 2 ou à 3; et R1 et R2 représentent chacun, séparément, un groupe éthyle, hydroxyéthyle ou hydroxyméthyle; ou R1 et R2 forment, conjointement avec l'atome d'azote auquel ils sont liés, un groupe cyclique tel qu'un groupe 1-pipéridino, 2- ou 4-(2-hydroxyéthyl)-1-pipéridino, 2-hydroxyméthyl-1-pipéridino, 4-(2-hydroxyéthyl)-pipérazino ou 4-méthyl-1-pipérazino ou 4-morpholino; ou à un sel pharmaceutiquement acceptable d'un tel composé. Ces composés sont utiles comme agents de lutte contre le cancer. Un procédé de préparation de ces composés ainsi que des compositions pharmaceutiques contenant ces composés sont également décrits.
• Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity
  作者：Soma Roy、Kalappa Muniyappa、Santanu Bhattacharya

  DOI：10.1002/cmdc.202200436

  日期：2022.11.18

  designed and synthesized ten new 2,6-disubstituted anthraquinone derivatives with various piperazinyl side chains. The structural differences between quadruplex and duplex DNA were used to probe these derivatives for the end-stacking mode of binding with G-quadruplex DNA. These ligands were found to trigger apoptosis, exhibiting selective cytotoxicity toward cancer cells over normal cells.

  基于蒽醌的化合物以其结合双链体和 G-四链体 DNA 的能力而闻名。研究此类化合物的成员如何特异性识别 G-四链体 DNA 而不是双链体 DNA 是一个重要的挑战。我们设计并合成了 10 种具有不同哌嗪基侧链的新型 2,6-二取代蒽醌衍生物。四链体和双链体 DNA 之间的结构差异用于探测这些衍生物与 G-四链体 DNA 结合的末端堆叠模式。发现这些配体会引发细胞凋亡，对癌细胞表现出比正常细胞更高的选择性细胞毒性。