(-)-3-(chloromethyl)-6-nitro-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline | 244087-97-6

• 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: (-)-3-(chloromethyl)-6-nitro-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline
• CAS: 244087-97-6
• 化学式: C₂₁H₂₀ClN₃O₆
• 分子量: 445.859
• InChiKey: AUXOUNCEXATLHW-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106.93
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (-)-3-(chloromethyl)-6-nitro-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline 在 platinum(IV) oxide 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以100%的产率得到(-)-6-amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline
  参考文献：
  名称：

  Cytotoxicity and DNA Interaction of the Enantiomers of 6-Amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline (Amino-seco-CI-TMI)

  摘要：

  The enantiomers of the previously reported racemic 6-amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline (amino-seco-CI-TMI) were prepared via resolution of a precursor by chiral HPLC. The only detectable product isolated from reaction of the racemic compound with calf thymus DNA, followed by thermal cleavage, was shown by mass spectrometry and two-dimensional NMR spectroscopy to be the adenine N3 adduct. Polyacrylamide gel electrophoresis assays with the racemate and with each enantiomer also showed adenine to be the only site of alkylation. While the racemic amino compound exhibited sequence selectivity identical to that of the previously characterized phenol analogue, the enantiomers exhibited distinctly different sequence selectivities, allowing the (+) enantiomer to be assigned the "natural" S configuration. The (+)-(S) enantiomer is 3-fold more cytotoxic than the (-)-(R) enantiomer (IC50 values of 240 and 700 nM, respectively, in AA8 cells, after exposure for 4 h).

  DOI：

  10.1021/tx990069o
• 作为产物：
  描述：

  (-)-1-(tert-butyloxycarbonyl)-3-[[(methylsulfonyl)oxy]methyl]-6-nitroindoline 在 盐酸 、 lithium chloride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 (-)-3-(chloromethyl)-6-nitro-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline
  参考文献：
  名称：

  Cytotoxicity and DNA Interaction of the Enantiomers of 6-Amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline (Amino-seco-CI-TMI)

  摘要：

  The enantiomers of the previously reported racemic 6-amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indoline (amino-seco-CI-TMI) were prepared via resolution of a precursor by chiral HPLC. The only detectable product isolated from reaction of the racemic compound with calf thymus DNA, followed by thermal cleavage, was shown by mass spectrometry and two-dimensional NMR spectroscopy to be the adenine N3 adduct. Polyacrylamide gel electrophoresis assays with the racemate and with each enantiomer also showed adenine to be the only site of alkylation. While the racemic amino compound exhibited sequence selectivity identical to that of the previously characterized phenol analogue, the enantiomers exhibited distinctly different sequence selectivities, allowing the (+) enantiomer to be assigned the "natural" S configuration. The (+)-(S) enantiomer is 3-fold more cytotoxic than the (-)-(R) enantiomer (IC50 values of 240 and 700 nM, respectively, in AA8 cells, after exposure for 4 h).

  DOI：

  10.1021/tx990069o