3-[(3,5-dimethylpyrrol-2-yl)methylidenyl]-1-(3-nitrophenylacetyl)indolin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-[(3,5-dimethylpyrrol-2-yl)methylidenyl]-1-(3-nitrophenylacetyl)indolin-2-one
• 英文别名: (3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1-[2-(3-nitrophenyl)acetyl]indol-2-one
• 化学式: C₂₃H₁₉N₃O₄
• 分子量: 401.422
• InChiKey: XVRNVSORHPYUQO-UYRXBGFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-硝基苯乙酸 、 3-[(3,5-二甲基-1H-吡咯-2-基)亚甲基]-1,3-二氢-2H-吲哚-2-酮 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 甲苯 为溶剂， 以6%的产率得到3-[(3,5-dimethylpyrrol-2-yl)methylidenyl]-1-(3-nitrophenylacetyl)indolin-2-one
  参考文献：
  名称：

  Synthesis of potential prodrug systems for reductive activation. Prodrugs for anti-angiogenic isoflavones and VEGF receptor tyrosine kinase inhibitory oxindoles

  摘要：

  A number of potential prodrug systems for reductive activation have been investigated. The prodrug systems chosen for the study were the 2-nitrophenylacetyl, 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoyl and 4-nitrobenzyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The drug molecules studied were the naturally occurring isoflavone biochanin A, an inhibitor of VEGF-induced angiogenesis, and the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its 6-hydroxy derivative, inhibitors of VEGF receptor tyrosine kinase. Following coupling the prodrug system to the drug, the compounds were evaluated chemically and biologically. Under chemical reducing conditions, the 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoic acid based prodrugs appear to fragment the most efficiently, followed by the 2-nitrophenylacetate esters with the 4-nitrobenzyl ethers being the least efficient. The potentially pro-anti-angiogenic compounds were also assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. Control compounds that cannot be activated under bioreductive conditions are less potent than the free drug, whereas many of the potential prodrugs not only exhibit a dose response, but appear at least equipotent with the free drug. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.04.014

文献信息

• Synthesis and evaluation of prodrugs for anti-angiogenic pyrrolylmethylidenyl oxindoles
  作者：Lesley Maskell、Emilie A. Blanche、Marie A. Colucci、Jacqueline L. Whatmore、Christopher J. Moody

  DOI：10.1016/j.bmcl.2006.12.108

  日期：2007.3

  Potential prodrugs of inhibitors of VEGF-induced angiogenesis have been investigated. The prodrug systems studied were the 4-nitrobenzyl, 2-nitrophenylacetyl and 3-methyl-3-(3,6-dimethylbenzo-1,4-quinon-2-yl)butanoyI groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The anti-angiogenic compounds studied were the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its novel 6-hydroxy derivative. The potentially pro-anti-angiogenic compounds were assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis of potential prodrug systems for reductive activation. Prodrugs for anti-angiogenic isoflavones and VEGF receptor tyrosine kinase inhibitory oxindoles
  作者：Emilie A. Blanche、Lesley Maskell、Marie A. Colucci、Jacqueline L. Whatmore、Christopher J. Moody

  DOI：10.1016/j.tet.2009.04.014

  日期：2009.6

  A number of potential prodrug systems for reductive activation have been investigated. The prodrug systems chosen for the study were the 2-nitrophenylacetyl, 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoyl and 4-nitrobenzyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The drug molecules studied were the naturally occurring isoflavone biochanin A, an inhibitor of VEGF-induced angiogenesis, and the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its 6-hydroxy derivative, inhibitors of VEGF receptor tyrosine kinase. Following coupling the prodrug system to the drug, the compounds were evaluated chemically and biologically. Under chemical reducing conditions, the 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoic acid based prodrugs appear to fragment the most efficiently, followed by the 2-nitrophenylacetate esters with the 4-nitrobenzyl ethers being the least efficient. The potentially pro-anti-angiogenic compounds were also assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. Control compounds that cannot be activated under bioreductive conditions are less potent than the free drug, whereas many of the potential prodrugs not only exhibit a dose response, but appear at least equipotent with the free drug. (C) 2009 Elsevier Ltd. All rights reserved.