EAPB0203 | 681284-86-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: EAPB0203
• 英文别名: N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine；EAPB203；Kxz9LA2QV7；N-methyl-1-(2-phenylethyl)imidazo[1,2-a]quinoxalin-4-amine
• CAS: 681284-86-6
• 化学式: C₁₉H₁₈N₄
• 分子量: 302.379
• InChiKey: HOACPUXUWCASLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  EAPB0203 在 氘代甲醇 作用下， 反应 2.0h， 生成
  参考文献：
  名称：

  Characterization of a New Anticancer Agent, EAPB0203, and Its Main Metabolites: Nuclear Magnetic Resonance and Liquid Chromatography–Mass Spectrometry Studies

  摘要：

  本研究旨在评估 EAPB0203 的主要未知含氧代谢物的结构。第一步是将 EAPB0203 及其去甲基化代谢物（EAPB0202）的所有 1H 和 13C NMR 归入其分子结构中的相应原子，并使用高分辨率质谱法（MS）阐明这些化合物的 [M + H]+ 离子的碎片路径。MS/MS 光谱显示，拥有偶数电子的质子化分子会意外地失去 H-、CH3- 甚至 C7H7- 等自由基，从而产生稳定的自由基阳离子。在大鼠和狗的肝脏微粒体以及丝状真菌 Cunninghamella elegans 中进行了体外代谢研究。根据以下几点对六种含氧代谢物进行了结构鉴定：(i) 它们在液相色谱-质谱/质谱（LC-MS/MS）分析中的碎片路径；(ii) 它们的分子质量和碎片离子变化与母体药物的分子质量和碎片离子变化的比较；以及 (iii) 在线 H/D 交换实验的结果，这些结果为区分氢氧基化代谢物和 N-氧化物提供了更多证据。代谢物的结构通过 LC-MS/MS 和与合成标准品的比较得以阐明；这些标准品的结构通过一维和二维 1H NMR 光谱得以确认。

  DOI：

  10.1021/ac3021483
• 作为产物：
  描述：

  (d,L)-4-苯基-2-羟基-1-丁胺 在 三甲基铵三氧化硫共聚物 、 三乙胺 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 73.0h， 生成 EAPB0203
  参考文献：
  名称：

  Design and synthesis of novel imidazo[1,2- a ]quinoxalines as PDE4 inhibitors

  摘要：

  New imidazo[1,2-a]quinoxaline derivatives have been synthesised by condensation of an appropriate alpha-aminoalcohol with a quinoxaline followed by intramolecular cyclisation and nucleophilic substitutions. Their phosphodiesterase inhibitory activities have been assessed on a preparation of the PDE4 isoform purified from a human alveolar epithelial cell line (A549). These studies showed potent inhibitory properties that emphasize the importance of a methyl amino group at position 4 and a weakly hindered group at position 1. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.11.034

文献信息

• IMIDAZOL[1,2-alpha]QUINOXALINES AND DERIVATIVES FOR THE TREATMENT OF CANCERS
  申请人：Deleuze-Masquefa Carine

  公开号：US20100249142A1

  公开（公告）日：2010-09-30

  Imidazo[1,2-a]quinoxaline compounds for the treatment of cancers as well as pharmaceutical compositions that include these compounds and their uses in therapy. The compound of general formula (I):

  咪唑并[1,2-a]喹噁啉化合物用于治疗癌症，以及包括这些化合物的药物组合物和它们在疗法中的用途。通式(I)的化合物：
• IMIDAZO[1,2-A]QUINOXALINES ET DÉRIVÉS POUR LE TRAITEMENT DES CANCERS
  申请人：Université de Montpellier

  公开号：EP2205602B1

  公开（公告）日：2018-09-26
• US8378098B2
  申请人：——

  公开号：US8378098B2

  公开（公告）日：2013-02-19
• Design and synthesis of novel imidazo[1,2- a ]quinoxalines as PDE4 inhibitors
  作者：Carine Deleuze-Masquéfa、Grégori Gerebtzoff、Guy Subra、Jean-Roch Fabreguettes、Annabel Ovens、Maëlle Carraz、Marie-Paule Strub、Jacques Bompart、Pascal George、Pierre-Antoine Bonnet

  DOI：10.1016/j.bmc.2003.11.034

  日期：2004.3

  New imidazo[1,2-a]quinoxaline derivatives have been synthesised by condensation of an appropriate alpha-aminoalcohol with a quinoxaline followed by intramolecular cyclisation and nucleophilic substitutions. Their phosphodiesterase inhibitory activities have been assessed on a preparation of the PDE4 isoform purified from a human alveolar epithelial cell line (A549). These studies showed potent inhibitory properties that emphasize the importance of a methyl amino group at position 4 and a weakly hindered group at position 1. (C) 2004 Elsevier Ltd. All rights reserved.
• Characterization of a New Anticancer Agent, EAPB0203, and Its Main Metabolites: Nuclear Magnetic Resonance and Liquid Chromatography–Mass Spectrometry Studies
  作者：Florian Lafaille、Bernard Banaigs、Nicolas Inguimbert、Christine Enjalbal、Pierre-Emmanuel Doulain、Pierre-Antoine Bonnet、Carine Masquefa、Françoise M.M. Bressolle

  DOI：10.1021/ac3021483

  日期：2012.11.20

  The present study was conducted to assess the structures of the main unknown oxygenated metabolites of EAPB0203. The first step was to assign all the 1H and 13C NMR of both EAPB0203 and its demethylated metabolite (EAPB0202) to the corresponding atoms in their molecular structures and to elucidate the fragmentation pathways for the [M + H]+ ions of these compounds using high-resolution mass spectrometry (MS). MS/MS spectra showed that both protonated molecules possessing an even number of electrons were unexpectedly losing radicals such as H•, CH3•, or even C7H7• giving stable radical cations. In vitro metabolism studies were investigated in rat and dog liver microsomes and in the filamentous fungus Cunninghamella elegans. Structural elucidation of six oxygenated metabolites was performed based on the following: (i) their fragmentation pathways in liquid chromatography–MS/MS (LC-MS/MS) analyses; (ii) comparison of their changes in their molecular masses and fragment ions with those of the parent drugs; and (iii) the results of online H/D exchange experiments that provided additional evidence in differentiating hydoxylated metabolites from N-oxides. Structures of the metabolites were elucidated by LC-MS/MS and comparison with synthetic standards; structures of these standards were confirmed using one- and two-dimensional 1H NMR spectroscopies.

  本研究旨在评估 EAPB0203 的主要未知含氧代谢物的结构。第一步是将 EAPB0203 及其去甲基化代谢物（EAPB0202）的所有 1H 和 13C NMR 归入其分子结构中的相应原子，并使用高分辨率质谱法（MS）阐明这些化合物的 [M + H]+ 离子的碎片路径。MS/MS 光谱显示，拥有偶数电子的质子化分子会意外地失去 H-、CH3- 甚至 C7H7- 等自由基，从而产生稳定的自由基阳离子。在大鼠和狗的肝脏微粒体以及丝状真菌 Cunninghamella elegans 中进行了体外代谢研究。根据以下几点对六种含氧代谢物进行了结构鉴定：(i) 它们在液相色谱-质谱/质谱（LC-MS/MS）分析中的碎片路径；(ii) 它们的分子质量和碎片离子变化与母体药物的分子质量和碎片离子变化的比较；以及 (iii) 在线 H/D 交换实验的结果，这些结果为区分氢氧基化代谢物和 N-氧化物提供了更多证据。代谢物的结构通过 LC-MS/MS 和与合成标准品的比较得以阐明；这些标准品的结构通过一维和二维 1H NMR 光谱得以确认。