4-methoxybenzyl 4-nitro-1-(trifluoromethanesulfonyloxy)naphthalene-2-carboxylate | 193225-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-methoxybenzyl 4-nitro-1-(trifluoromethanesulfonyloxy)naphthalene-2-carboxylate
• 英文别名: 4-methoxybenzyl 4-nitro-1-trifluoromethylsulfonyloxynaphthalene-2-carboxylate；(4-methoxyphenyl)methyl 4-nitro-1-(trifluoromethylsulfonyloxy)naphthalene-2-carboxylate
• CAS: 193225-56-8
• 化学式: C₂₀H₁₄F₃NO₈S
• 分子量: 485.394
• InChiKey: PWUQEYXDKKCROX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  133
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-methoxybenzyl 4-nitro-1-(trifluoromethanesulfonyloxy)naphthalene-2-carboxylate 在 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1--4-nitronaphthalene-2-carboxylic acid
  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-羟基萘-2-羧酸钠盐 在 硝酸 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 4-methoxybenzyl 4-nitro-1-(trifluoromethanesulfonyloxy)naphthalene-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
• 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.