1-[2-(2-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylamino}-ethoxy)-ethyl]-pyrrole-2,5-dione | 872356-56-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 1-[2-(2-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylamino}-ethoxy)-ethyl]-pyrrole-2,5-dione
• CAS: 872356-56-4
• 化学式: C₃₅H₃₈N₂O₁₄
• 分子量: 710.692
• InChiKey: ZWCKVWMSGQXYJR-SYXQFFNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.43
• 重原子数：
  51.0
• 可旋转键数：
  12.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  238.69
• 氢给体数：
  6.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  (3S)-3-amino-4-oxo-4-(2-sulfanylethylamino)butanoic acid 、 1-[2-(2-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylamino}-ethoxy)-ethyl]-pyrrole-2,5-dione 以 二甲基亚砜 为溶剂， 反应 0.5h， 以44%的产率得到(3S)-3-amino-4-[2-[1-[2-[2-[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]ethoxy]ethyl]-2,5-dioxopyrrolidin-3-yl]sulfanylethylamino]-4-oxobutanoic acid
  参考文献：
  名称：

  The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

  摘要：

  The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3'-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3'-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.046
• 作为产物：
  描述：

  1-[2-(2-羟基乙氧基)乙基]吡咯-2,5-二酮 在 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 1-[2-(2-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylamino}-ethoxy)-ethyl]-pyrrole-2,5-dione
  参考文献：
  名称：

  The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

  摘要：

  The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3'-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3'-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.046