(11aS)-11-hydroxy-7-methoxy-8-([3-{5-[5-(5-methoxycarbonyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl]-ethoxy)-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester | 909415-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (11aS)-11-hydroxy-7-methoxy-8-([3-{5-[5-(5-methoxycarbonyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl]-ethoxy)-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (6S,6aS)-6-hydroxy-2-methoxy-3-[3-[[5-[[5-[(5-methoxycarbonyl-1-methylpyrrol-3-yl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropoxy]-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
• CAS: 909415-12-9
• 化学式: C₄₀H₄₈N₈O₁₁
• 分子量: 816.868
• InChiKey: OGHOPQDECWINTQ-UGOHAPBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  59
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  217
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (11aS)-11-hydroxy-7-methoxy-8-([3-{5-[5-(5-methoxycarbonyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl]-ethoxy)-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 3.0h， 以96%的产率得到(11aS) methyl 4-{[4-({4-[4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)propionylamino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  WO2007/39752

  摘要：

  公开号：
• 作为产物：
  描述：

  L-脯氨醇 在 palladium on activated charcoal 4-二甲氨基吡啶 、 重铬酸吡啶 、 4 A molecular sieve 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -30.0~20.0 ℃ 、110.32 kPa 条件下， 反应 50.0h， 生成 (11aS)-11-hydroxy-7-methoxy-8-([3-{5-[5-(5-methoxycarbonyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl]-ethoxy)-5-oxo-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biophysical and Biological Evaluation of a Series of Pyrrolobenzodiazepine−Poly(N-methylpyrrole) Conjugates

  摘要：

  A novel series of methyl ester-terminated C8-linked pyrrolobenzodiazepine (PBD)-poly(N-methylpyrrole) conjugates (50a-f) has been synthesized and their DNA interaction evaluated by thermal denaturation, DNA footprinting, and in vitro transcription stop assays. The synergistic effect of attaching a PBD unit to a polypyrrole fragment is illustrated by the large increase in DNA binding affinity (up to 50-fold) compared to the individual PBD and pyrrole components. 50a-f were found to bind mainly to identical DNA sequences but with apparent binding site widths increasing with molecular length and the majority of sites conforming to the consensus motif 5'-XGXW(z) (z = 3 +/- 1; W = A or T; X = any base but preferably a purine). They also provided robust sequence-selective blockade of transcription at sites corresponding approximately to their DNA footprints. 50a-f were shown to have good cellular/ nuclear penetration properties, and a degree of correlation between cytotoxicity and DNA-binding affinity was observed.

  DOI：

  10.1021/jm051199z