prop-2-enyl N-[(5S)-5-[[(2S)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-[4-(hydroxymethyl)anilino]-6-oxohexyl]carbamate | 1387556-13-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: prop-2-enyl N-[(5S)-5-[[(2S)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-[4-(hydroxymethyl)anilino]-6-oxohexyl]carbamate
• CAS: 1387556-13-9
• 化学式: C₃₃H₄₄N₆O₈
• 分子量: 652.748
• InChiKey: JGIOTAFJMBYZDN-WWEDSPNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  47
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  204
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  prop-2-enyl N-[(5S)-5-[[(2S)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-[4-(hydroxymethyl)anilino]-6-oxohexyl]carbamate 在 吡啶 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 36.0h， 生成 [4-[[(2S)-2-[[(2S)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-(prop-2-enoxycarbonylamino)hexanoyl]amino]phenyl]methyl (3aS,4S,6R,7aS)-4-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-2,3a,4,6,7,7a-hexahydropyrano[4,3-d][1,3]oxazole-1-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Characterization of Protease-Activated Prodrugs of Doxazolidine

  摘要：

  Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthesis and characterization of a prodrug platform designed for doxaz release mediated by secreted proteolytic activity, a common association with invasiveness and poor prognosis in cancer patients. GaFK-Doxaz is hydrolyzable by the proteases plasmin and cathepsin B, both strongly linked with cancer progression, as well as trypsin. We demonstrate that activation of GaFK-Doxaz releases highly potent doxaz that powerfully inhibits the growth of a wide variety of cancer cells (average IC50 of 8 nM). GaFK-Doxaz is stable in human plasma and is poorly membrane permeable, thereby limiting activation to locally secreted proteolytic activity and reducing the likelihood of severe side effects.

  DOI：

  10.1021/jm300714p
• 作为产物：
  描述：

  、 2-(羧基氨基)乙酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-D-丙氨酸 、 N-[(9H-芴-9-甲氧基)羰基]-N'-[(2-丙烯氧基)羰基]-L-赖氨酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 prop-2-enyl N-[(5S)-5-[[(2S)-2-[[(2R)-2-[(2-acetamidoacetyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-6-[4-(hydroxymethyl)anilino]-6-oxohexyl]carbamate
  参考文献：
  名称：

  Synthesis and Biological Characterization of Protease-Activated Prodrugs of Doxazolidine

  摘要：

  Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthesis and characterization of a prodrug platform designed for doxaz release mediated by secreted proteolytic activity, a common association with invasiveness and poor prognosis in cancer patients. GaFK-Doxaz is hydrolyzable by the proteases plasmin and cathepsin B, both strongly linked with cancer progression, as well as trypsin. We demonstrate that activation of GaFK-Doxaz releases highly potent doxaz that powerfully inhibits the growth of a wide variety of cancer cells (average IC50 of 8 nM). GaFK-Doxaz is stable in human plasma and is poorly membrane permeable, thereby limiting activation to locally secreted proteolytic activity and reducing the likelihood of severe side effects.

  DOI：

  10.1021/jm300714p

文献信息

• Design and Synthesis of New Protease‐Triggered CO‐Releasing Peptide–Metal‐Complex Conjugates
  作者：Nikolay S. Sitnikov、Yulia B. Malysheva、Alexey Yu. Fedorov、Hans‐Günther Schmalz

  DOI：10.1002/ejoc.201901206

  日期：2019.10.31

  Potentially tissue‐selective protease‐activated CO‐releasing molecules (PT‐CORMs) were designed and synthesized by conjugating a protease‐specifying peptide to an oxy‐cyclohexadiene‐Fe(CO)3 unit through a self‐immolative linker.

  设计和合成了潜在的组织选择性蛋白酶激活的CO释放分子（PT-CORM），方法是通过自消灭性接头将蛋白酶特异性肽与氧-环己二烯-Fe（CO）3单元缀合。