(11S,11aS)-8-(2-{2-[4-Amino-1-(2-chloro-ethyl)-naphthalen-2-ylcarbamoyl]-benzofuran-5-ylcarbamoyl}-ethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid 2,2,2-trichloro-ethyl ester | 914909-80-1

• 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: (11S,11aS)-8-(2-{2-[4-Amino-1-(2-chloro-ethyl)-naphthalen-2-ylcarbamoyl]-benzofuran-5-ylcarbamoyl}-ethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid 2,2,2-trichloro-ethyl ester
• CAS: 914909-80-1
• 化学式: C₄₀H₃₇Cl₄N₅O₉
• 分子量: 873.574
• InChiKey: AHDVRINGGCMLCY-HTOJEEBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.87
• 重原子数：
  58.0
• 可旋转键数：
  11.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  185.9
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (11S,11aS)-8-(2-{2-[4-Amino-1-(2-chloro-ethyl)-naphthalen-2-ylcarbamoyl]-benzofuran-5-ylcarbamoyl}-ethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid 2,2,2-trichloro-ethyl ester 在 cadmium lead 乙酸铵 作用下， 以 四氢呋喃 为溶剂， 以84%的产率得到5-[3-((S)-7-Methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yloxy)-propionylamino]-benzofuran-2-carboxylic acid [4-amino-1-(2-chloro-ethyl)-naphthalen-2-yl]-amide
  参考文献：
  名称：

  DNA interstrand crosslinking agents: Synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD)

  摘要：

  The design and synthesis of three novel bisalkylating agents derived from the achiral seco-duocarmycin or CC-1065 analogs and pyrrolobenzodiazepines (PBDs) are described: achiral seco-CBI (cyclopropanebenz[e]indoline)-PBD 11, achiral seco-CI-PBD 12, and achiral seco-CBI dimer 13. Compounds 11 and 12 demonstrated enhanced cytotoxicity over the monomer counterparts against the growth of PS 15 murine mastocytoma cells in culture. Conjugate 11 was found to covalently react with adenine-N3 positions within the minor groove at AT-rich sequences and to produce DNA interstrand crosslinks. Both compounds were found to induce apoptosis in P815 cells. Due to its poor water solubility, dimer 13 did not give any appreciable DNA binding or cytotoxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.005
• 作为产物：
  描述：

  2-[2-amino-4-(N-tert-butoxycarbonylamino)naphthalen-1-yl]ethyl acetate 在 palladium on activated charcoal 吡啶 、 盐酸 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (11S,11aS)-8-(2-{2-[4-Amino-1-(2-chloro-ethyl)-naphthalen-2-ylcarbamoyl]-benzofuran-5-ylcarbamoyl}-ethoxy)-11-hydroxy-7-methoxy-5-oxo-2,3,11,11a-tetrahydro-1H,5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carboxylic acid 2,2,2-trichloro-ethyl ester
  参考文献：
  名称：

  DNA interstrand crosslinking agents: Synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD)

  摘要：

  The design and synthesis of three novel bisalkylating agents derived from the achiral seco-duocarmycin or CC-1065 analogs and pyrrolobenzodiazepines (PBDs) are described: achiral seco-CBI (cyclopropanebenz[e]indoline)-PBD 11, achiral seco-CI-PBD 12, and achiral seco-CBI dimer 13. Compounds 11 and 12 demonstrated enhanced cytotoxicity over the monomer counterparts against the growth of PS 15 murine mastocytoma cells in culture. Conjugate 11 was found to covalently react with adenine-N3 positions within the minor groove at AT-rich sequences and to produce DNA interstrand crosslinks. Both compounds were found to induce apoptosis in P815 cells. Due to its poor water solubility, dimer 13 did not give any appreciable DNA binding or cytotoxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.005