2-(2-Azidocarbonyl-4-nitro-naphthalen-1-yl)-malonic acid dimethyl ester | 1028275-97-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(2-Azidocarbonyl-4-nitro-naphthalen-1-yl)-malonic acid dimethyl ester
• 英文别名: Dimethyl 2-(2-carbonazidoyl-4-nitronaphthalen-1-yl)propanedioate
• CAS: 1028275-97-9
• 化学式: C₁₆H₁₂N₄O₇
• 分子量: 372.294
• InChiKey: YAMVDTJPTLUZPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  130
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(2-Azidocarbonyl-4-nitro-naphthalen-1-yl)-malonic acid dimethyl ester 以 甲苯 为溶剂， 生成 1,1-di(methoxycarbonyl)-5-nitro-1,3-dihydro-2H-benzindol-2-one
  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：

  4-methoxybenzyl 4-nitro-1-(trifluoromethanesulfonyloxy)naphthalene-2-carboxylate 在 吡啶 、 氯化亚砜 、 sodium azide 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-(2-Azidocarbonyl-4-nitro-naphthalen-1-yl)-malonic acid dimethyl ester
  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 amino analogues of the potent DNA alkylating agent seco-CBI-TMI
  作者：G.J. Atwell、W.R. Wilson、W.A. Denny

  DOI：10.1016/s0960-894x(97)00259-x

  日期：1997.6

  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.
• 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.