6-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid | 1075719-58-2

• 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: 6-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid
• 英文别名: (2S,3S,4S,5R,6S)-6-[[2-[(4-acetamidobenzoyl)amino]phenyl]carbamoyloxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 1075719-58-2
• 化学式: C₂₂H₂₃N₃O₁₀
• 分子量: 489.439
• InChiKey: OAMBPTZVSFFXSW-CURYNPBISA-N

物化性质

• 熔点：
  194 °C
• 沸点：
  720.0±60.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  204
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-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-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-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以80%的产率得到6-[2-(4-acetylamino-benzoylamino)-phenylcarbamoyloxy]-3,4,5-trihydroxy-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

文献信息

• Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy
  作者：Mickaël Thomas、Jonathan Clarhaut、Isabelle Tranoy-Opalinski、Jean-Pierre Gesson、Joëlle Roche、Sébastien Papot

  DOI：10.1016/j.bmc.2008.07.048

  日期：2008.9

  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.