methyl [3-formyl-2-pentyl-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate | 618881-41-7

• 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: methyl [3-formyl-2-pentyl-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate
• 英文别名: methyl[3-formyl-2-pentyl-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate；Methyl 3-formyl-5-methyl-2-pentyl-1-(2-phenylethyl)indole-6-carboxylate
• CAS: 618881-41-7
• 化学式: C₂₅H₂₉NO₃
• 分子量: 391.51
• InChiKey: IVTIMFIUCUPQRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl [3-formyl-2-pentyl-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 生成 methyl [3-hydroxymethyl-2-(1-pentyl)-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate
  参考文献：
  名称：

  Small molecule inhibition of a PDZ-domain interaction

  摘要：

  已发现的新型化合物可有效抑制PDZ结构域相互作用，特别是MAGIs中的PDZ结构域与肿瘤抑制蛋白PTEN之间的相互作用，以及Dishevelled（Dvl）蛋白中的PDZ结构域与其他蛋白如Frizzled（Fz）蛋白之间的相互作用，其一般公式如下。该发明还包括用这些化合物进行筛选和研究蛋白的组合库、阵列和方法。该发明的化合物已在过度表达Dishevelled蛋白（Dvl）的某些细胞系中诱导细胞凋亡；抑制Wnt信号传导。

  公开号：

  US20050043385A1
• 作为产物：
  描述：

  2-甲基-5-硝基苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal 、 copper(l) iodide 、 二(氰基苯)二氯化钯 、 氢气 、 一氯化碘 、 caesium carbonate 、 二乙胺 、 calcium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.33h， 生成 methyl [3-formyl-2-pentyl-1-(2-phenylethyl)-5-methyl]indole-6-carboxylate
  参考文献：
  名称：

  A Selective Irreversible Inhibitor Targeting a PDZ Protein Interaction Domain

  摘要：

  Irreversible inhibitors of proteases have proven themselves useful tools for determining which proteases are active under given conditions in tissues or cells and for studying the functional role that a protease plays in physiological processes. The application of such techniques to the study of the activity and function of protein-protein interactions has been hindered by the lack of guiding principles for the mechanistic design of irreversible inhibitors targeting the "active site" of a protein interaction. We report herein the first example of a mechanism-based irreversible inhibitor of a protein interaction that has been specifically targeted to one member of the PDZ family of protein interaction domains: the second PDZ domain of the membrane-associated guanylate kinase MAGI3. This inhibitor was designed using rationally directed computational evaluation to take advantage of a conserved histidine in the PDZ domain by introducing an ionizable group that will be held in close proximity to that nucleophile during binding. The novel compound exhibits all of the characteristics of an irreversible inhibitor of the interaction of the tumor suppressor PTEN with MAGI3 in in vitro models. In cells, the inhibitor can be shown to release PTEN from sequestration by MAGI3 and consequently upregulate the PKB signaling pathway.

  DOI：

  10.1021/ja035540l

文献信息

• Small molecule inhibition of a PDZ-domain interaction
  申请人：Guy Kiplin R.

  公开号：US20050043385A1

  公开（公告）日：2005-02-24

  Novel compounds that have been found effective in inhibiting PDZ domain interactions, and particularly interactions of PDZ domains in MAGIs with the oncogenic (tumor suppressor) protein PTEN and interactions between the PDZ domain in the Dishevelled (Dvl) protein and other proteins such as the Frizzled (Fz) protein, have the general formula The invention also includes combinatorial libraries, arrays and methods for screening and studying proteins using such compounds. Compounds of the invention have produced apoptosis in certain cell lines that overexpress the Dishevelled protein (Dvl); inhibiting Wnt signaling.

  已发现的新型化合物可有效抑制PDZ结构域相互作用，特别是MAGIs中的PDZ结构域与肿瘤抑制蛋白PTEN之间的相互作用，以及Dishevelled（Dvl）蛋白中的PDZ结构域与其他蛋白如Frizzled（Fz）蛋白之间的相互作用，其一般公式如下。该发明还包括用这些化合物进行筛选和研究蛋白的组合库、阵列和方法。该发明的化合物已在过度表达Dishevelled蛋白（Dvl）的某些细胞系中诱导细胞凋亡；抑制Wnt信号传导。
• US7601750B2
  申请人：——

  公开号：US7601750B2

  公开（公告）日：2009-10-13
• A Selective Irreversible Inhibitor Targeting a PDZ Protein Interaction Domain
  作者：Naoaki Fujii、Jose J. Haresco、Kathleen A. P. Novak、David Stokoe、Irwin D. Kuntz、R. Kiplin Guy

  DOI：10.1021/ja035540l

  日期：2003.10.1

  Irreversible inhibitors of proteases have proven themselves useful tools for determining which proteases are active under given conditions in tissues or cells and for studying the functional role that a protease plays in physiological processes. The application of such techniques to the study of the activity and function of protein-protein interactions has been hindered by the lack of guiding principles for the mechanistic design of irreversible inhibitors targeting the "active site" of a protein interaction. We report herein the first example of a mechanism-based irreversible inhibitor of a protein interaction that has been specifically targeted to one member of the PDZ family of protein interaction domains: the second PDZ domain of the membrane-associated guanylate kinase MAGI3. This inhibitor was designed using rationally directed computational evaluation to take advantage of a conserved histidine in the PDZ domain by introducing an ionizable group that will be held in close proximity to that nucleophile during binding. The novel compound exhibits all of the characteristics of an irreversible inhibitor of the interaction of the tumor suppressor PTEN with MAGI3 in in vitro models. In cells, the inhibitor can be shown to release PTEN from sequestration by MAGI3 and consequently upregulate the PKB signaling pathway.