1-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline | 185433-55-0

• 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-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline
• 英文别名: 1-(t-Butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline；1-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindoline；tert-butyl 3-(chloromethyl)-6-nitro-2,3-dihydroindole-1-carboxylate
• CAS: 185433-55-0
• 化学式: C₁₄H₁₇ClN₂O₄
• 分子量: 312.753
• InChiKey: KIDSZNLTRZMEIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline 在 platinum(IV) oxide 盐酸 、 氢气 、 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 、 1,4-二氧六环 为溶剂， 反应 29.75h， 生成 Amino MMI-CI
  参考文献：
  名称：

  Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-seco-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity

  摘要：

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.

  DOI：

  10.1021/jm980545s
• 作为产物：
  描述：

  (+/-)-1-(tert-butyloxycarbonyl)-3-[[(methylsulfonyl)oxy]methyl]-6-nitroindoline 在 三乙胺 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 1-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline
  参考文献：
  名称：

  Tercel, Moana; Denny, William A., Journal of the Chemical Society. Perkin transactions I, 1998, # 3, p. 509 - 519

  摘要：

  DOI：

文献信息

• Cyclopropylindoles and their seco precursors, and their use as prodrugs
  申请人：Cancer Research Campaign Technology Limited

  公开号：US05985909A1

  公开（公告）日：1999-11-16

  The present invention provides compounds of formula (I) and (II) which may be used as anticancer drugs.

  本发明提供了化合物(I)和(II)的公式，可用作抗癌药物。
• A novel nitro-substituted seco-CI: Application as a reductively activated adept prodrug
  作者：M. Tercel、W.A. Denny、W.R. Wilson

  DOI：10.1016/s0960-894x(96)00508-2

  日期：1996.11

  An alternative synthesis of seco-CI alkylating agents bearing a nitrogen substituent at C-6 is reported. The nitro compound 3 prepared by this route exhibits a 400-fold increase in cytotoxicity against UV4 cells in the presence of a nitroreductase enzyme from Escherichia coli B, suggesting it as a potential prodrug for use in antibody-directed enzyme prodrug therapy. Copyright (C) 1996 Elsevier Science Ltd
• CYCLOPROPYLINDOLES AND THEIR SECO PRECURSORS, AND THEIR USE AS PRODRUGS
  申请人：AUCKLAND DIVISION CANCER SOCIETY OF NEW ZEALAND INC.

  公开号：EP0850220A1

  公开（公告）日：1998-07-01
• SECO PRECURSORS OF CYCLOPROPYLINDOLINES AND THEIR USE AS PRODRUGS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：EP0944596A1

  公开（公告）日：1999-09-29
• 1-ACRYLOYLINDOLINE DERIVATIVES AND THEIR USE AS PRODRUGS OF ANTICANCER AGENTS
  申请人：Auckland Uniservices Limited

  公开号：EP0944596B1

  公开（公告）日：2002-10-16