1-<(E)-4-butyramido-1-methyl-2-pyrroleacryloyl>-3-(chloromethyl)-6-nitroindoline | 209046-41-3

• 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: 1-<(E)-4-butyramido-1-methyl-2-pyrroleacryloyl>-3-(chloromethyl)-6-nitroindoline
• 英文别名: (E)-1-(4-Butyramido-1-methyl-2-pyrroleacryloyl)-3-chloromethyl-6-nitroindoline；N-[5-[(E)-3-[3-(chloromethyl)-6-nitro-2,3-dihydroindol-1-yl]-3-oxoprop-1-enyl]-1-methylpyrrol-3-yl]butanamide
• CAS: 209046-41-3
• 化学式: C₂₁H₂₃ClN₄O₄
• 分子量: 430.891
• InChiKey: ZDFHNKMHWNQKTB-SOFGYWHQSA-N

物化性质

• 熔点：
  205-207 °C
• 沸点：
  645.420±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.352±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<(E)-4-butyramido-1-methyl-2-pyrroleacryloyl>-3-(chloromethyl)-6-nitroindoline 在 铁粉 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以69%的产率得到6-Amino-1[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-chloromethylindoline
  参考文献：
  名称：

  Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-seco-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity

  摘要：

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.

  DOI：

  10.1021/jm980545s
• 作为产物：
  描述：

  1-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 21.0h， 生成 1-<(E)-4-butyramido-1-methyl-2-pyrroleacryloyl>-3-(chloromethyl)-6-nitroindoline
  参考文献：
  名称：

  Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-seco-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity

  摘要：

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.

  DOI：

  10.1021/jm980545s

文献信息

• Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-<i>seco</i>-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity
  作者：Jared B. J. Milbank、Moana Tercel、Graham J. Atwell、William R. Wilson、Alison Hogg、William A. Denny

  DOI：10.1021/jm980545s

  日期：1999.2.1

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.