[2-amino-5-methoxy-4-(4-{2-methoxy-4-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-3-isoxazolyl]phenoxy}butoxy)phenyl]{(2S)-2-[di(ethylsulfanyl)methyl]tetrahydro-1H-1-pyrrolyl}methanone | 1189742-41-3

• 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: [2-amino-5-methoxy-4-(4-{2-methoxy-4-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-3-isoxazolyl]phenoxy}butoxy)phenyl]{(2S)-2-[di(ethylsulfanyl)methyl]tetrahydro-1H-1-pyrrolyl}methanone
• CAS: 1189742-41-3
• 化学式: C₄₀H₅₃N₃O₉S₂
• 分子量: 784.008
• InChiKey: FQKWYWXIIBPGNP-TZYYSAMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.85
• 重原子数：
  54.0
• 可旋转键数：
  20.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  132.53
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  [2-amino-5-methoxy-4-(4-{2-methoxy-4-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-3-isoxazolyl]phenoxy}butoxy)phenyl]{(2S)-2-[di(ethylsulfanyl)methyl]tetrahydro-1H-1-pyrrolyl}methanone 在 calcium carbonate 、 mercury dichloride 作用下， 以 水 、 乙腈 为溶剂， 反应 12.0h， 以362 mg的产率得到(11aS)-7-(methyloxy)-8-{4-[(2-(methyloxy)-4-{5-[3,4,5-tri(methyloxy)phenyl]-4,5-dihydro-3-isoxazolyl}phenyl)oxy]butyloxy}-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepi-5-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents

  摘要：

  A series of 3,5-diaryl-isoxazoline/isoxazole linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates were prepared. These conjugates showed potent anticancer activity with GI(50) values in the range of <0.1-3.6 mu M. Some of these PBD conjugates (6a-c) with promising anticancer activity were further investigated on the cell cycle distribution. Moreover, these PBD conjugates exhibited G0/G1 arrest, enhancement in the levels of p53 protein as well as mitochondrial-mediated intrinsic pathway, leading to release of cytochrome c, activation of caspase-3, cleavage of PARP and subsequent apoptotic cell death. Hence these PBD conjugates with 6a being the most potent one could be be taken up for preclinical studies either alone or in combination with existing therapies. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.047
• 作为产物：
  描述：

  [(2S)-2-[di(ethylsulfanyl)methyl]tetrahydro-1H-pyrrol-1-yl]-[5-methoxy-4-(4-{2-methoxy-4-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-3-isoxazolyl]phenoxy}butoxy)-2-nitrophenyl]methanone 在 tin(II) chloride dihdyrate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 [2-amino-5-methoxy-4-(4-{2-methoxy-4-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-3-isoxazolyl]phenoxy}butoxy)phenyl]{(2S)-2-[di(ethylsulfanyl)methyl]tetrahydro-1H-1-pyrrolyl}methanone
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents

  摘要：

  A series of 3,5-diaryl-isoxazoline/isoxazole linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates were prepared. These conjugates showed potent anticancer activity with GI(50) values in the range of <0.1-3.6 mu M. Some of these PBD conjugates (6a-c) with promising anticancer activity were further investigated on the cell cycle distribution. Moreover, these PBD conjugates exhibited G0/G1 arrest, enhancement in the levels of p53 protein as well as mitochondrial-mediated intrinsic pathway, leading to release of cytochrome c, activation of caspase-3, cleavage of PARP and subsequent apoptotic cell death. Hence these PBD conjugates with 6a being the most potent one could be be taken up for preclinical studies either alone or in combination with existing therapies. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.047