1,1-di(methoxycarbonyl)-5-nitro-1,2-dihydro-3H-benzindole | 193225-60-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1,1-di(methoxycarbonyl)-5-nitro-1,2-dihydro-3H-benzindole
• 英文别名: Dimethyl 5-nitro-2,3-dihydrobenzo[e]indole-1,1-dicarboxylate
• CAS: 193225-60-4
• 化学式: C₁₆H₁₄N₂O₆
• 分子量: 330.297
• InChiKey: YEECXRDYBLFPQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,1-di(methoxycarbonyl)-5-nitro-1,2-dihydro-3H-benzindole 在 吡啶 、 N-甲基咪唑 、 sodium methylate 、 二异丁基氢化铝 、 甲基磺酰氯 、 三氟乙酸 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzindole
  参考文献：
  名称：

  Synthesis and cytotoxicity of amino analogues of the potent DNA alkylating agent seco-CBI-TMI

  摘要：

  The synthesis of racemic seco-CBI-TMI analogues containing nitrogen-based groups in place of the 5-OH is reported, employing a synthetic strategy where the incipient C-5 amino substituent is generated in the last step from a nitro precursor. The resulting amino seco-CBI analogues are up to 1000-fold more potent cytotoxins than the corresponding known amino seco-CI compounds, making them attractive candidates as effecters in prodrug strategies. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00259-x
• 作为产物：
  描述：

  1,1-di(methoxycarbonyl)-5-nitro-1,3-dihydro-2H-benzindol-2-one 在 2,3-二巯基丁二酸 、 硼烷 作用下， 以 四氢呋喃 为溶剂， 以57%的产率得到1,1-di(methoxycarbonyl)-5-nitro-1,2-dihydro-3H-benzindole
  参考文献：
  名称：

  Synthesis and cytotoxicity of amino analogues of the potent DNA alkylating agent seco-CBI-TMI

  摘要：

  The synthesis of racemic seco-CBI-TMI analogues containing nitrogen-based groups in place of the 5-OH is reported, employing a synthetic strategy where the incipient C-5 amino substituent is generated in the last step from a nitro precursor. The resulting amino seco-CBI analogues are up to 1000-fold more potent cytotoxins than the corresponding known amino seco-CI compounds, making them attractive candidates as effecters in prodrug strategies. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00259-x

文献信息

• Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3<i>H</i>-benz[<i>e</i>]indole (Amino-<i>s</i><i>eco</i>-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents
  作者：Graham J. Atwell、Moana Tercel、Maruta Boyd、William R. Wilson、William A. Denny

  DOI：10.1021/jo981395w

  日期：1998.12.1

  The first synthesis of seco-CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15-step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2-0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.
• CYCLOPROPYLINDOLE COMPOUNDS AND THEIR USE AS PRODRUGS
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP0938474B1

  公开（公告）日：2005-11-23