6-benzyloxy-3-hydroxymethyl-N-methanesulfonyl-2,3-dihydro-1H-indole | 173368-77-9

• 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: 6-benzyloxy-3-hydroxymethyl-N-methanesulfonyl-2,3-dihydro-1H-indole
• 英文别名: (1-Methylsulfonyl-6-phenylmethoxy-2,3-dihydroindol-3-yl)methanol
• CAS: 173368-77-9
• 化学式: C₁₇H₁₉NO₄S
• 分子量: 333.408
• InChiKey: HMWUSVHBXKSGCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-benzyloxy-3-hydroxymethyl-N-methanesulfonyl-2,3-dihydro-1H-indole 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 红铝 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 20.0~60.0 ℃ 、300.0 kPa 条件下， 反应 55.0h， 生成 (3R/S)-3-(tert-butyldiphenylsilyl)oxymethyl-6-hydroxy-1-(5',6',7'-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indole
  参考文献：
  名称：

  A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs

  摘要：

  Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00098-0
• 作为产物：
  描述：

  3-acetoxymethyl-2,3-dihydro-1-methylsulfonyl-6-methoxyindole 在 甲醇 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 44.5h， 生成 6-benzyloxy-3-hydroxymethyl-N-methanesulfonyl-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Tietze, Lutz F.; Hannemann, Robert; Buhr, Wilm, Angewandte Chemie, 1996, vol. 108, # 22, p. 2840 - 2842

  摘要：

  DOI：

文献信息

• US4590280A
  申请人：——

  公开号：US4590280A

  公开（公告）日：1986-05-20
• A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs
  作者：Lutz F. Tietze、Monika Lieb、Tobias Herzig、Frank Haunert、Ingrid Schuberth

  DOI：10.1016/s0968-0896(01)00098-0

  日期：2001.7

  Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Tietze, Lutz F.; Hannemann, Robert; Buhr, Wilm, Angewandte Chemie, 1996, vol. 108, # 22, p. 2840 - 2842
  作者：Tietze, Lutz F.、Hannemann, Robert、Buhr, Wilm、Loegers, Michael、Menningen, Pia、et al.

  DOI：——

  日期：——