3-[(5-methoxy-indole-2-yl)carbonyl]-1-(chloromethyl)-1,2dihydro-3H-benz[e]indole | 454713-42-9

• 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: 3-[(5-methoxy-indole-2-yl)carbonyl]-1-(chloromethyl)-1,2dihydro-3H-benz[e]indole
• 英文别名: ICT2803；[1-(chloromethyl)-1,2-dihydrobenzo[e]indol-3-yl]-(5-methoxy-1H-indol-2-yl)methanone
• CAS: 454713-42-9
• 化学式: C₂₃H₁₉ClN₂O₂
• 分子量: 390.869
• InChiKey: ZQZDMDZWAZDAIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  tert-butyl (1-bromonaphthalen-2-yl)carbamate 在 盐酸 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 、 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 、 甲苯 、 mineral oil 为溶剂， 反应 21.25h， 生成 3-[(5-methoxy-indole-2-yl)carbonyl]-1-(chloromethyl)-1,2dihydro-3H-benz[e]indole
  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

• Benz-indole and benzo-quinoline derivatives as prodrugs for tumor treatment
  申请人：——

  公开号：US20040138246A1

  公开（公告）日：2004-07-15

  Compounds of the general formula (I) or (IA) in which X is H, Y is a leaving group, R 1 preferably being an aromatic DNA binding subunit are prodrug analogues of duocarmycin. The compounds are expected to be hydroxylated at the carbon atom to which X is joined, by cytochrome P450, in particular by CYP1B1, expressed at high levels in tumours. The prodrug is expected to be activated preferentially in tumour cells, where it will act as a DNA alkylating agent preventing cell division. 1

  通式（I）或（IA）的化合物，其中 X 为 H，Y 为离去基团，R 1 最好是芳香族 DNA 结合亚基，它们是都卡霉素的原药类似物。预计这些化合物会在 X 所连接的碳原子上被细胞色素 P450，特别是肿瘤中高水平表达的 CYP1B1 所羟化。预计原药将优先在肿瘤细胞中被激活，在那里它将作为一种 DNA 烷基化剂阻止细胞分裂。 1
• BENZ-INDOLE AND BENZO-QUINOLINE DERIVATIVES AS PRODRUGS FOR TUMOUR TREATMENT
  申请人：SCHOOL OF PHARMACY, UNIVERSITY OF LONDON

  公开号：EP1408960B1

  公开（公告）日：2006-05-31
• US7192977B2
  申请人：——

  公开号：US7192977B2

  公开（公告）日：2007-03-20
• US8017640B2
  申请人：——

  公开号：US8017640B2

  公开（公告）日：2011-09-13
• 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.