prop-2-enyl (2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate | 1374694-32-2

• 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: prop-2-enyl (2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate
• CAS: 1374694-32-2
• 化学式: C₉₁H₁₁₇N₇O₄₁
• 分子量: 1964.95
• InChiKey: QELXZKUYFMNLOB-ZJLWVDPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  139
• 可旋转键数：
  71
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  605
• 氢给体数：
  7
• 氢受体数：
  43

反应信息

• 作为反应物：
  描述：

  prop-2-enyl (2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate 在 四(三苯基膦)钯 、 苯胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以40%的产率得到(2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin

  摘要：

  In this paper we describe the synthesis and biological evaluation of the first beta-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.

  DOI：

  10.1021/jm300348r
• 作为产物：
  描述：

  6-(马来酰亚胺基)己酸琥珀酰亚胺酯 、 prop-2-enyl (2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate 以 二甲基亚砜 为溶剂， 反应 16.0h， 以166 mg的产率得到prop-2-enyl (2S,3S,4S,5R,6S)-6-[4-[2-[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]-1-[[(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]carbamoyloxy]ethyl]-2-nitrophenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate
  参考文献：
  名称：

  Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin

  摘要：

  In this paper we describe the synthesis and biological evaluation of the first beta-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.

  DOI：

  10.1021/jm300348r

文献信息

• Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin
  作者：Thibaut Legigan、Jonathan Clarhaut、Brigitte Renoux、Isabelle Tranoy-Opalinski、Arnaud Monvoisin、Jean-Marc Berjeaud、François Guilhot、Sébastien Papot

  DOI：10.1021/jm300348r

  日期：2012.5.10

  In this paper we describe the synthesis and biological evaluation of the first beta-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.