trifluoromethanesulfonic acid 7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indol-5-yl ester | 1092796-43-4

• 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: trifluoromethanesulfonic acid 7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indol-5-yl ester
• 英文别名: [7,8-dimethoxy-2-[(4-methoxyphenyl)methyl]-10-methyl-1-oxo-3H-azepino[3,4-b]indol-5-yl] trifluoromethanesulfonate
• CAS: 1092796-43-4
• 化学式: C₂₄H₂₃F₃N₂O₇S
• 分子量: 540.517
• InChiKey: FQUOKVQFULXFGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  trifluoromethanesulfonic acid 7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indol-5-yl ester 、 4-羟基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲苯 、 乙醇 为溶剂， 反应 1.5h， 以78%的产率得到5-(4-hydroxyphenyl)-7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-3,10-dihydro-2H-azepino[3,4-b]indol-1-one
  参考文献：
  名称：

  Synthesis, Modeling, and RET Protein Kinase Inhibitory Activity of 3- and 4-Substituted β-Carbolin-1-ones

  摘要：

  A series of beta-carbolin-2-ones and 3,10-dihydro-2H-azepino[3,4-b]indol-1-ones have been designed, synthesized, and evaluated as RET protein kinase inhibitors oil the basis Of their Structural similarity with the prototype indolin-2-one RPI-1. Some beta-carbolin-2-ones (structure 2) showed ail ability to inhibit RET enzymatic activity in vitro and proliferation of RETC634R oncogene-transformed NIH3T3 cells comparable to that of the reference compound. The docking analysis of the interaction of these compounds with the crystallographic structure of RET tyrosine kinase domain suggested a new binding interaction scheme different from the one proposed during their design. The rigid structure of the compounds of this series represents a new scaffold with potential advantages in the design of RET protein kinase inhibitors.

  DOI：

  10.1021/jm8007823
• 作为产物：
  描述：

  三氟甲磺酸酐 、 7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-3,4-dihydro-2H,10H-azepino[3,4-b]indole-1,5-dione 在 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 以28%的产率得到trifluoromethanesulfonic acid 7,8-dimethoxy-2-(4-methoxybenzyl)-10-methyl-1-oxo-1,2,3,10-tetrahydroazepino[3,4-b]indol-5-yl ester
  参考文献：
  名称：

  Synthesis, Modeling, and RET Protein Kinase Inhibitory Activity of 3- and 4-Substituted β-Carbolin-1-ones

  摘要：

  A series of beta-carbolin-2-ones and 3,10-dihydro-2H-azepino[3,4-b]indol-1-ones have been designed, synthesized, and evaluated as RET protein kinase inhibitors oil the basis Of their Structural similarity with the prototype indolin-2-one RPI-1. Some beta-carbolin-2-ones (structure 2) showed ail ability to inhibit RET enzymatic activity in vitro and proliferation of RETC634R oncogene-transformed NIH3T3 cells comparable to that of the reference compound. The docking analysis of the interaction of these compounds with the crystallographic structure of RET tyrosine kinase domain suggested a new binding interaction scheme different from the one proposed during their design. The rigid structure of the compounds of this series represents a new scaffold with potential advantages in the design of RET protein kinase inhibitors.

  DOI：

  10.1021/jm8007823

文献信息

• Synthesis, Modeling, and RET Protein Kinase Inhibitory Activity of 3- and 4-Substituted β-Carbolin-1-ones
  作者：Raffaella Cincinelli、Giuliana Cassinelli、Sabrina Dallavalle、Cinzia Lanzi、Lucio Merlini、Maurizio Botta、Tiziano Tuccinardi、Adriano Martinelli、Sergio Penco、Franco Zunino

  DOI：10.1021/jm8007823

  日期：2008.12.25

  A series of beta-carbolin-2-ones and 3,10-dihydro-2H-azepino[3,4-b]indol-1-ones have been designed, synthesized, and evaluated as RET protein kinase inhibitors oil the basis Of their Structural similarity with the prototype indolin-2-one RPI-1. Some beta-carbolin-2-ones (structure 2) showed ail ability to inhibit RET enzymatic activity in vitro and proliferation of RETC634R oncogene-transformed NIH3T3 cells comparable to that of the reference compound. The docking analysis of the interaction of these compounds with the crystallographic structure of RET tyrosine kinase domain suggested a new binding interaction scheme different from the one proposed during their design. The rigid structure of the compounds of this series represents a new scaffold with potential advantages in the design of RET protein kinase inhibitors.