5,6-dimethoxy-1-methyl-1H-indole-2-carboxylic acid [3-(4-methoxy-phenyl)-3-oxopropyl]-amide | 1092796-49-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5,6-dimethoxy-1-methyl-1H-indole-2-carboxylic acid [3-(4-methoxy-phenyl)-3-oxopropyl]-amide
• 英文别名: 5,6-dimethoxy-N-[3-(4-methoxyphenyl)-3-oxopropyl]-1-methylindole-2-carboxamide
• CAS: 1092796-49-0
• 化学式: C₂₂H₂₄N₂O₅
• 分子量: 396.443
• InChiKey: DMYVJHGNZDQXAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,6-dimethoxy-1-methyl-1H-indole-2-carboxylic acid [3-(4-methoxy-phenyl)-3-oxopropyl]-amide 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 生成 7,8-dimethoxy-5-(4-methoxyphenyl)-10-methyl-3,10-dihydro-2H-azepino[3,4-b]indol-1-one
  参考文献：
  名称：

  分子内N-酰基亚胺离子与Friedel-Crafts在3-吲哚上的环化：新型吡咯并[2,1- b ]吲哚和同系物的合成

  摘要：

  吲哚-2-羧酸β-和γ-氧代酰胺的酸处理导致Friedel-Crafts分子内环化为β-咔啉酮和二氢-2 H-氮杂环庚烷[3,4- b ]吲哚-1-酮，与仲δ相反-，ɛ-和ζ-氧代酰胺，可环化成新型杂环吡咯并[2,1- b ]吲哚，吲哚并[2,1- b ]吲哚和9a，11-二氮杂茚并[1,2-通过中间的N-酰基亚胺离子形成α ] azulene。叔酰胺仅导致Friedel-Crafts环闭合，从而允许合成更大的稠合环。

  DOI：

  10.1016/j.tet.2009.02.036
• 作为产物：
  描述：

  5,6-dimethoxy-1-methyl-1H-indole-2-carboxylic acid 、 3-amino-1-(4-methoxyphenyl)propan-1-one trifluoromethanesulfonate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以56%的产率得到5,6-dimethoxy-1-methyl-1H-indole-2-carboxylic acid [3-(4-methoxy-phenyl)-3-oxopropyl]-amide
  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.
• Intramolecular N-acyliminium ion versus Friedel–Crafts cyclization onto 3-indoles: synthesis of the novel rings pyrrolizino[2,1-b]indole and homologues
  作者：Raffaella Cincinelli、Sabrina Dallavalle、Lucio Merlini、Raffaella Nannei、Leonardo Scaglioni

  DOI：10.1016/j.tet.2009.02.036

  日期：2009.4

  γ-oxoamides causes Friedel–Crafts intramolecular cyclization to β-carbolinones and dihydro-2H-azepino[3,4-b]indol-1-ones, in contrast to secondary δ-,ɛ-, and ζ-oxoamides, which cyclize to the novel heterocyclic rings pyrrolizino[2,1-b]indole, indolizino[2,1-b]indole, and 9a,11-diaza-indeno[1,2-a]azulene, via an intermediate N-acyliminium ion. Tertiary amides lead only the Friedel–Crafts ring closure, thus

  吲哚-2-羧酸β-和γ-氧代酰胺的酸处理导致Friedel-Crafts分子内环化为β-咔啉酮和二氢-2 H-氮杂环庚烷[3,4- b ]吲哚-1-酮，与仲δ相反-，ɛ-和ζ-氧代酰胺，可环化成新型杂环吡咯并[2,1- b ]吲哚，吲哚并[2,1- b ]吲哚和9a，11-二氮杂茚并[1,2-通过中间的N-酰基亚胺离子形成α ] azulene。叔酰胺仅导致Friedel-Crafts环闭合，从而允许合成更大的稠合环。