(1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indol-3(6H)-yl)(5-fluoro-1H-indol-2-yl)methanone | 1449381-26-3

• 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: (1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indol-3(6H)-yl)(5-fluoro-1H-indol-2-yl)methanone
• 英文别名: ICT2705；[8-(chloromethyl)-7,8-dihydro-3H-pyrrolo[3,2-e]indol-6-yl]-(5-fluoro-1H-indol-2-yl)methanone
• CAS: 1449381-26-3
• 化学式: C₂₀H₁₅ClFN₃O
• 分子量: 367.81
• InChiKey: AAYVYSQBZXEGNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  51.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  tert-butyl 5-amino-4-bromo-1H-indole-1-carboxylate 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三(三甲基硅基)硅烷 、 sodium hydride 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 32.75h， 生成 (1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indol-3(6H)-yl)(5-fluoro-1H-indol-2-yl)methanone
  参考文献：
  名称：

  Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity

  摘要：

  A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds was synthesized and used to probe selective activation by cells expressing CYP1A1 and 2W1, CYPs known to be expressed in high frequency in some tumors. Several CPI-based compounds were pM-nM potent in CYP1A1 expressing cells. CYP2W1 was also shown to sensitize proliferating cells to several compounds, demonstrating its potential as a target for tumor selective activation of duocarmycin bioprecursors.

  DOI：

  10.1021/jm4000209

文献信息

• Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug
  作者：Christoffer Bengtsson、Ylva Gravenfors

  DOI：10.3390/molecules28124818

  日期：——

  development of a short and convenient synthesis of a type of duocarmycin prodrug. The 1,2,3,6-tetrahydropyrrolo[3,2-e]indole-containing core is here constructed from commercially available Boc-5-bromoindole in four steps and 23% overall yield, utilizing a Buchwald–Hartwig amination followed by a sodium hydride-induced regioselective bromination. In addition, protocols for selective mono- and di-halogenations

  双卡霉素类化合物的构建通常与冗长的合成路线相关。本文提出了一种多卡霉素前药的短且方便的合成方法的开发。此处，含有 1,2,3,6-四氢吡咯并[3,2-e]吲哚的核心是由市售的 Boc-5-溴吲哚构建而成，采用 Buchwald-Hartwig 胺化，然后进行胺化，分四步，总产率为 23%。氢化钠诱导的区域选择性溴化。此外，还开发了位置 3 和位置 4 的选择性单卤化和二卤化方案，这可能有助于进一步探索该支架。
• Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity
  作者：Helen M. Sheldrake、Sandra Travica、Inger Johansson、Paul M. Loadman、Mark Sutherland、Lina Elsalem、Nicola Illingworth、Alexander J. Cresswell、Tristan Reuillon、Steven D. Shnyder、Souren Mkrtchian、Mark Searcey、Magnus Ingelman-Sundberg、Laurence H. Patterson、Klaus Pors

  DOI：10.1021/jm4000209

  日期：2013.8.8

  A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds was synthesized and used to probe selective activation by cells expressing CYP1A1 and 2W1, CYPs known to be expressed in high frequency in some tumors. Several CPI-based compounds were pM-nM potent in CYP1A1 expressing cells. CYP2W1 was also shown to sensitize proliferating cells to several compounds, demonstrating its potential as a target for tumor selective activation of duocarmycin bioprecursors.