6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid | 1075719-57-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid
• 英文别名: (2S,3S,4S,5R,6S)-6-[4-[[2-[(4-acetamidobenzoyl)amino]phenyl]carbamoyloxymethyl]-2-nitrophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 1075719-57-1
• 化学式: C₂₉H₂₈N₄O₁₃
• 分子量: 640.56
• InChiKey: HMMZYVVHGLJUKZ-CPIYQPHESA-N

物化性质

• 熔点：
  161.6 °C
• 沸点：
  876.7±65.0 °C(Predicted)
• 密度：
  1.625±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  259
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid 在 Escherichia coli β-glucuronidase 作用下， 以 phosphate buffer 为溶剂， 生成 (1S,2S)-安非他酮N-1’-脱氧-beta-D-葡萄糖醛酸 、 二氧化碳 、 4-羟基-3-硝基苄醇 、 4-乙酰氨基-N-(2'-氨基苯基)-苯甲酰胺
  参考文献：
  名称：

  Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy

  摘要：

  Two glucuronide prodrugs of the histone deacetylase inhibitor CI-994 were synthesized. These compounds were found to be soluble in aqueous media and stable under physiological conditions. The carbamoyl derivatisation of CI-994 significantly decreased its toxicity towards NCI-H661 lung cancer cells. Prodrug incubation with beta-glucuronidase in the culture media led efficiently to the release of the parent drug and thereby restoring its ability to decrease cell proliferation, to inhibit HDAC and to induce E-Cadherin expression. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.048
• 作为产物：
  描述：

  6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 0.25h， 以51 mg的产率得到6-{4-[(2-(4-acetylamino-benzoylamino)-phenylcarbamoyl)oxymethyl]-2-nitro-phenoxy}-tetrahydro-2H-pyran-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy

  摘要：

  Two glucuronide prodrugs of the histone deacetylase inhibitor CI-994 were synthesized. These compounds were found to be soluble in aqueous media and stable under physiological conditions. The carbamoyl derivatisation of CI-994 significantly decreased its toxicity towards NCI-H661 lung cancer cells. Prodrug incubation with beta-glucuronidase in the culture media led efficiently to the release of the parent drug and thereby restoring its ability to decrease cell proliferation, to inhibit HDAC and to induce E-Cadherin expression. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.048