1-{[2-(dimethylamino-N-oxide)ethyl]amino}-4-{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione | 221216-02-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1-{[2-(dimethylamino-N-oxide)ethyl]amino}-4-{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione
• 英文别名: 1-{[2-(dimethylamino-N-oxide)ethyl]amino}-4-{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-one；NSC684664；P28UP6P9DZ；2-[[4-[2-(dimethylamino)ethylamino]-5,8-dihydroxy-9,10-dioxoanthracen-1-yl]amino]-N,N-dimethylethanamine oxide
• CAS: 221216-02-0
• 化学式: C₂₂H₂₈N₄O₅
• 分子量: 428.488
• InChiKey: DQFZXLFASNTVCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1,4-Bis{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione bis-N-oxide 在 cytochrome P₄₅₀ reductase 、 extrahepatic P₄₅₀ enzyme CYP₂S₁ 、 甲酸铵 、 nicotinamide adenine dinucleotide phosphate 作用下， 以 乙腈 为溶剂， 生成 化合物 AQ4 、 1-{[2-(dimethylamino-N-oxide)ethyl]amino}-4-{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione
  参考文献：
  名称：

  Efficient Hypoxic Activation of the Anticancer Agent AQ4N by CYP2S1 and CYP2W1

  摘要：

  AQ4N [1,4-双{[2-(二甲氨基-N-氧化物)乙基]氨基}-5,8-二羟基蒽-9,10-二酮]，一种具有两个二甲氨基N-氧化物基团的前药，被转化为拓扑异构酶 II 抑制剂 AQ4 [1,4-双{[2-(二甲氨基)乙基]氨基}-5,8-二羟基-蒽-9,10-二酮]通过将 N-氧化物还原为二甲氨基取代基。早期研究表明，几种药物代谢细胞色素 P450 (P450) 酶可以在与实体瘤中类似的缺氧条件下催化这种还原反应。 CYP2S1和CYP2W1是从人类基因组中鉴定出的两种功能未知的肝外P450酶，它们在缺氧肿瘤细胞中的表达水平比正常组织中高得多。在这里，我们证明，与已发表的报告（Mol Pharmacol 76：1031-1043，2009）相反，CYP2S1 可以被 NADPH-P450 还原酶有效还原。最重要的是，与之前研究的所有 P450 酶相比，CYP2S1 和 CYP2W1 都是 AQ4N 还原活化为 AQ4 的更好催化剂。 CYP2S1和CYP2W1在肿瘤组织中的过度表达，以及它们对AQ4N激活的高催化活性，表明它们可用于抗癌前药的局部激活。

  DOI：

  10.1124/mol.110.065045

文献信息

• Reductive Heme-Dependent Activation of the <i>N</i>-Oxide Prodrug AQ4N by Nitric Oxide Synthase
  作者：Clinton R. Nishida、Paul R. Ortiz de Montellano

  DOI：10.1021/jm800496s

  日期：2008.8.1

  Anaerobic reduction of anticancer prodrugs is a promising route to achieve targeting and selectivity in anticancer drug design. Most reductive prodrug activations involve simple electron transfer from a flavoprotein and are not amenable to specific targeting. Here, we report that the N-oxide AQ4N is reduced by a nitric oxide synthase. This reduction involves interaction with the heme iron atom in the active site and is thus subject to specific protein constraints.
• Formulations of anthraquinone derivatives
  申请人：Halbert William Gavin

  公开号：US20070027136A1

  公开（公告）日：2007-02-01

  A stable, sterile aqueous solution of a compound of formula (I): in which A is a C alkylene group with a chain length between NH and N(O)R′R″ of at least 2 carbon atoms and R′ and R″ are each separately selected from C 1-4 alkyl groups and C 2-4 hydroxyalkyl and C 2-4 dihydroxyalkyl groups, or R′ and R″ together are a C 2-6 alkylene group, is formulated in a unit dosage form in a sealed container, said solution having a concentration of the compound of formula (I) up to 150 mg/ml and a pH in the range of 5 to 9. The solution may be prepared without a freeze drying step.
• Process for the preparation of aq4n
  申请人：Matthews Timothy William Ian

  公开号：US20070161808A1

  公开（公告）日：2007-07-12

  A process for the preparation of compound AQ4N of formula (2) or a salt or solvate thereof wherein the said process includes the reaction step: Formula (1), Formula (2), where compound AQ4 of formula (1) is oxidised to compound AQ4N of formula (2) with an oxidising agent at a reaction temperature not exceeding 10° C.
• US7276537B2
  申请人：——

  公开号：US7276537B2

  公开（公告）日：2007-10-02