4-methoxybenzyl 1--4-nitronaphthalene-2-carboxylate | 193225-57-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-methoxybenzyl 1--4-nitronaphthalene-2-carboxylate
• 英文别名: 4-methoxybenzyl 1-[di(methoxycarbonyl)methyl]-4-nitronaphthalene-2-carboxylate；dimethyl 2-[2-[(4-methoxyphenyl)methoxycarbonyl]-4-nitronaphthalen-1-yl]propanedioate
• CAS: 193225-57-9
• 化学式: C₂₄H₂₁NO₉
• 分子量: 467.432
• InChiKey: AWFTVIOIKSKUKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-methoxybenzyl 1--4-nitronaphthalene-2-carboxylate 在 palladium on activated charcoal 二苯基磷酸 、 氢气 、 苯甲醚 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 三氟乙酸 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 13.67h， 生成 5-amino-1,1-di(methoxycarbonyl)-1,2-dihydro-3H-benzisoindol-3-one
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3H-benz[e]indole (Amino-seco-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents

  摘要：

  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.

  DOI：

  10.1021/jo981395w
• 作为产物：
  描述：

  1-羟基萘-2-羧酸钠盐 在 硝酸 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-methoxybenzyl 1--4-nitronaphthalene-2-carboxylate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3H-benz[e]indole (Amino-seco-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents

  摘要：

  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.

  DOI：

  10.1021/jo981395w

文献信息

• Condensed N-aclyindoles as antitumor agents
  申请人：Cancer Research Campaign Technology Limited

  公开号：US06130237A1

  公开（公告）日：2000-10-10

  The invention provides compounds of general formula (I), wherein: X is halogen or OSO.sub.2 R, where R represents H or is unsubstituted or hydroxy-or amino-substituted lower alkyl; Y is a nitro or amine group or a substituted derivative thereof; W is selected from the structures of formulae (Ia, Ib or Ic), where E is --N.dbd. or --CH.dbd., G is O, S, or NH, and Q is either up to three of R, OR, NRR, NO.sub.2, CONHR, NHCOR or NHCONHR, or is an additional group of formulae (Ia, Ib or Ic) and HET represents a 5- or 6-membered carbocycle or heterocycle; and A and B collectively represent a fused benzene or 2-CO.sub.2 R pyrrole ring. In one embodiment, the group Y is an amine derivative substituted by a group which is a substrate for a nitroreductase or carboxypeptidase enzyme such that one of said enzymes is able to bring about removal of that group. ##STR1##

  该发明提供了一般式(I)的化合物，其中：X是卤素或OSO.sub.2 R，其中R代表H或未取代或羟基或氨基取代的较低烷基；Y是一个硝基或胺基团或其取代衍生物；W从式(Ia、Ib或Ic)的结构中选择，其中E为--N.dbd.或--CH.dbd.，G为O、S或NH，Q为R、OR、NRR、NO.sub.2、CONHR、NHCOR或NHCONHR中的最多三个，或者是式(Ia、Ib或Ic)的附加基团，HET代表一个5-或6-成员的碳环或杂环；A和B共同代表一个融合的苯或2-CO.sub.2 R吡咯环。在一个实施例中，基团Y是由一种基团取代的胺衍生物，该基团是一种硝基还原酶或羧肽酶酶的底物，使得其中一种酶能够去除该基团。
• 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.
• 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
• US6130237A
  申请人：——

  公开号：US6130237A

  公开（公告）日：2000-10-10
• [EN] CYCLOPROPYLINDOLE COMPOUNDS AND THEIR USE AS PRODRUGS<br/>[FR] COMPOSES DE CYCLOPROPYLINDOLE ET UTILISATION DE CES DERNIERS EN QUALITE DE PRECURSEURS DE MEDICAMENTS
  申请人：——

  公开号：WO1998011101A2

  公开（公告）日：1998-03-19

  [EN] The invention provides compounds of general formula (I), wherein: X is halogen or OSO2R, where R represents H or is unsubstituted or hydroxy- or amino-substituted lower alkyl; Y is a nitro or amine group or a substituted derivative thereof; W is selected from the structures of formulae (Ia, Ib or Ic), where E is -N= or -CH=, G is O, S, or NH, and Q is either up to three of R, OR, NRR, NO2, CONHR, NHCOR or NHCONHR, or is an additional group of formulae (Ia, Ib or Ic) and HET represents a 5- or 6-membered carbocycle or heterocycle; and A and B collectively represent a fused benzene or 2-CO2R pyrrole ring. In one embodiment, the group Y is an amine derivative substituted by a group which is a substrate for a nitroreductase or carboxypeptidase enzyme such that one of said enzymes is able to bring about removal of that group.
  [FR] Cette invention concerne des composés correspondant à la formule générale (I) où X représente halogène ou OSO2R dans lequel R représente H ou un alkyle inférieur non substitué ou substitué par hydroxy ou amino. Y représente un groupe amine ou nitro ou un dérivé substitué de ces derniers. W est choisi parmi les structures correspondant aux formules (Ia), (Ib) ou (Ic) où E représente -N= ou -CH=. G représente O, S ou NH, tandis que Q représente soit trois éléments au maximum choisis dans le groupe R, OR, NRR, NO2, CONHR, NHCOR ou NHCONHR, soit un groupe complémentaire des formules (Ia), (Ib) ou (Ic). HET représente un hétérocycle ou un carbocycle comportant de 5 à 6 membres, tandis que A et B représentent ensemble un benzène fusionné ou un anneau pyrrole 2-CO2R. Dans un mode de réalisation, le groupe Y représente un dérivé d'amine qui est substitué par un groupe consistant en un substrat pour une enzyme de type nitroréductase ou carboxypeptidase, ceci de manière à ce que l'une de ces enzymes puisse entraîner l'élimination de ce groupe.