(11S,11aS)-7-methoxy-8-[3-(5-methoxycarbonyl-1-methyl-1H-pyrrol-3-ylcarbamoyl)propoxy]-5-oxo-11-(tetrahydropyran-2-yloxy)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid allyl ester | 909415-20-9

• 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: (11S,11aS)-7-methoxy-8-[3-(5-methoxycarbonyl-1-methyl-1H-pyrrol-3-ylcarbamoyl)propoxy]-5-oxo-11-(tetrahydropyran-2-yloxy)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid allyl ester
• 英文别名: (11aS) methyl 4-[4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butyryIamino]-1-methyl-1H-pyrrole-2-carboxylate；prop-2-enyl (6S,6aS)-2-methoxy-3-[4-[(5-methoxycarbonyl-1-methylpyrrol-3-yl)amino]-4-oxobutoxy]-6-(oxan-2-yloxy)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
• CAS: 909415-20-9
• 化学式: C₃₃H₄₂N₄O₁₀
• 分子量: 654.717
• InChiKey: FOKGEPPPFRHEFB-VPDPRHMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (11S,11aS)-7-methoxy-8-[3-(5-methoxycarbonyl-1-methyl-1H-pyrrol-3-ylcarbamoyl)propoxy]-5-oxo-11-(tetrahydropyran-2-yloxy)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid allyl ester 在 四(三苯基膦)钯 四氢吡咯 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以83%的产率得到(11aS) methyl 4-[4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butyrylamino]-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：

  5-methoxy-4-(4-methoxy-4-oxobutoxy)-2-nitrobenzoic acid 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 草酰氯 、 氢气 、 对甲苯磺酸 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -40.0~70.0 ℃ 、275.79 kPa 条件下， 反应 62.25h， 生成 (11S,11aS)-7-methoxy-8-[3-(5-methoxycarbonyl-1-methyl-1H-pyrrol-3-ylcarbamoyl)propoxy]-5-oxo-11-(tetrahydropyran-2-yloxy)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carboxylic acid allyl 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