methyl 4-iodo-5-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]-1H-indole-2-carboxylate | 204916-07-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 4-iodo-5-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]-1H-indole-2-carboxylate
• CAS: 204916-07-4
• 化学式: C₁₈H₂₁IN₂O₄
• 分子量: 456.28
• InChiKey: JGQNBTHELOGPFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-iodo-5-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]-1H-indole-2-carboxylate 在 platinum(IV) oxide 盐酸 、 氢气 、 硝酸 、 三正丁基氢锡 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium chloride 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 硝基甲烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 80.0 ℃ 、344.74 kPa 条件下， 反应 169.01h， 生成 (R)-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：

  3-amino-2-iodobenzyl acetate 在 manganese(IV) oxide 、 sodium hexamethyldisilazane 、 sodium hydride 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 84.33h， 生成 methyl 4-iodo-5-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]-1H-indole-2-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

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