2-iodo-3-nitrobenzyl acetate | 204915-99-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-iodo-3-nitrobenzyl acetate
• 英文别名: (2-Iodo-3-nitrophenyl)methyl acetate
• CAS: 204915-99-1
• 化学式: C₉H₈INO₄
• 分子量: 321.071
• InChiKey: HYZNAHCBJSMZLR-UHFFFAOYSA-N

物化性质

• 熔点：
  64-65 °C
• 沸点：
  371.6±32.0 °C(Predicted)
• 密度：
  1.822±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-iodo-3-nitrobenzyl acetate 在 platinum(IV) oxide 盐酸 、 manganese(IV) oxide 、 氢气 、 硝酸 、 三正丁基氢锡 、 sodium hexamethyldisilazane 、 铁粉 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 甲基磺酰氯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 锌 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 甲醇 、 硝基甲烷 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 xylene 为溶剂， -78.0~80.0 ℃ 、344.74 kPa 条件下， 反应 109.42h， 生成 methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Amino-seco-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA

  摘要：

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.

  DOI：

  10.1021/jo990464j
• 作为产物：
  描述：

  2-碘-3-硝基-苯甲酸 在 4-二甲氨基吡啶 、 硼酸三甲酯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.67h， 生成 2-iodo-3-nitrobenzyl acetate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Amino-seco-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA

  摘要：

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.

  DOI：

  10.1021/jo990464j

文献信息

• 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.
• Synthesis and Cytotoxicity of Amino-<i>s</i><i>eco</i>-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA
  作者：Moana Tercel、Michael A. Gieseg、William A. Denny、William R. Wilson

  DOI：10.1021/jo990464j

  日期：1999.8.1

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.