di-tert-butyl 1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate | 1350890-87-7

• 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: di-tert-butyl 1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate
• 英文别名: Ditert-butyl 8-(chloromethyl)-7,8-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate；ditert-butyl 8-(chloromethyl)-7,8-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate
• CAS: 1350890-87-7
• 化学式: C₂₁H₂₇ClN₂O₄
• 分子量: 406.909
• InChiKey: DWISKPQRVUCMMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  di-tert-butyl 1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 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
• 作为产物：
  描述：

  5-硝基吲哚 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三(三甲基硅基)硅烷 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 45.42h， 生成 di-tert-butyl 1-(chloromethyl)-1,2-dihydropyrrolo[3,2-e]indole-3,6-dicarboxylate
  参考文献：
  名称：

  Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity

  摘要：

  确定一种能被细胞色素 P450（CYP）选择性激活的药物，有可能实现组织特异性剂量强化，从而显著提高其治疗价值。为实现这一目标，我们公布了一种双霉素类似物 ICT2700 的活化途径证据，它以 CYP1A1 为靶点，具有生物活性。

  DOI：

  10.1039/c1cc15638a

文献信息

• Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity
  作者：Klaus Pors、Paul M. Loadman、Steven D. Shnyder、Mark Sutherland、Helen M. Sheldrake、Meritxell Guino、Konstantinos Kiakos、John A. Hartley、Mark Searcey、Laurence H. Patterson

  DOI：10.1039/c1cc15638a

  日期：——

  The identification of an agent that is selectively activated by a cytochrome P450 (CYP) has the potential for tissue specific dose intensification as a means of significantly improving its therapeutic value. Towards this goal, we disclose evidence for the pathway of activation of a duocarmycin analogue, ICT2700, which targets CYP1A1 for biological activity.

  确定一种能被细胞色素 P450（CYP）选择性激活的药物，有可能实现组织特异性剂量强化，从而显著提高其治疗价值。为实现这一目标，我们公布了一种双霉素类似物 ICT2700 的活化途径证据，它以 CYP1A1 为靶点，具有生物活性。
• 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.